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1.	Cederwall, Bo, et al. (författare) Evidence for a spin-aligned neutron-proton paired phase from the level structure of 92Pd 2011 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 469:7328, s. 68-71 Tidskriftsartikel (refereegranskat)abstract Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work(1) that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing(2-6), in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus Pd-92. Gamma rays emitted following the Ni-58(Ar-36,2n)Pd-92 fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution c-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction(2-6). We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling(7,8)) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.
2.	Kehoe, Laura, et al. (författare) Make EU trade with Brazil sustainable 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
3.	Boen, Rune, et al. (författare) Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers 2024 Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160 Tidskriftsartikel (refereegranskat)abstract Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
4.	Tjernström, Michael, et al. (författare) The Arctic Summer Cloud Ocean Study (ASCOS) : overview and experimental design 2014 Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:6, s. 2823-2869 Tidskriftsartikel (refereegranskat)abstract The climate in the Arctic is changing faster than anywhere else on earth. Poorly understood feedback processes relating to Arctic clouds and aerosol-cloud interactions contribute to a poor understanding of the present changes in the Arctic climate system, and also to a large spread in projections of future climate in the Arctic. The problem is exacerbated by the paucity of research-quality observations in the central Arctic. Improved formulations in climate models require such observations, which can only come from measurements in situ in this difficult-to-reach region with logistically demanding environmental conditions. The Arctic Summer Cloud Ocean Study (ASCOS) was the most extensive central Arctic Ocean expedition with an atmospheric focus during the International Polar Year (IPY) 2007-2008. ASCOS focused on the study of the formation and life cycle of low-level Arctic clouds. ASCOS departed from Longyearbyen on Svalbard on 2 August and returned on 9 September 2008. In transit into and out of the pack ice, four short research stations were undertaken in the Fram Strait: two in open water and two in the marginal ice zone. After traversing the pack ice northward, an ice camp was set up on 12 August at 87 degrees 21' N, 01 degrees 29' W and remained in operation through 1 September, drifting with the ice. During this time, extensive measurements were taken of atmospheric gas and particle chemistry and physics, mesoscale and boundary-layer meteorology, marine biology and chemistry, and upper ocean physics. ASCOS provides a unique interdisciplinary data set for development and testing of new hypotheses on cloud processes, their interactions with the sea ice and ocean and associated physical, chemical, and biological processes and interactions. For example, the first-ever quantitative observation of bubbles in Arctic leads, combined with the unique discovery of marine organic material, polymer gels with an origin in the ocean, inside cloud droplets suggests the possibility of primary marine organically derived cloud condensation nuclei in Arctic stratocumulus clouds. Direct observations of surface fluxes of aerosols could, however, not explain observed variability in aerosol concentrations, and the balance between local and remote aerosols sources remains open. Lack of cloud condensation nuclei (CCN) was at times a controlling factor in low-level cloud formation, and hence for the impact of clouds on the surface energy budget. ASCOS provided detailed measurements of the surface energy balance from late summer melt into the initial autumn freeze-up, and documented the effects of clouds and storms on the surface energy balance during this transition. In addition to such process-level studies, the unique, independent ASCOS data set can and is being used for validation of satellite retrievals, operational models, and reanalysis data sets.
5.	De Palma, Adriana, et al. (författare) Predicting bee community responses to land-use changes : effects of geographic and taxonomic biases 2016 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6, s. 1-14 Tidskriftsartikel (refereegranskat)abstract Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
6.	Kaufmann, Tobias, et al. (författare) Common brain disorders are associated with heritable patterns of apparent aging of the brain 2019 Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617- Tidskriftsartikel (refereegranskat)abstract Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
7.	Carleo, Ilaria, et al. (författare) The Multiplanet System TOI-421* 2020 Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3 Tidskriftsartikel (refereegranskat)abstract We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
8.	Carlström, Mattias, et al. (författare) L-arginine or tempol supplementation improves renal and cardiovascular function in rats with reduced renal mass and chronic high salt intake 2013 Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 207:4, s. 732-741 Tidskriftsartikel (refereegranskat)abstract Aim Early life reduction in nephron number and chronic high salt intake cause development of renal and cardiovascular disease, which has been associated with oxidative stress and nitric oxide (NO) deficiency. We investigated the hypothesis that interventions stimulating NO signalling or reducing oxidative stress may restore renal autoregulation, attenuate hypertension and reduce renal and cardiovascular injuries following reduction in renal mass and chronic high salt intake. Methods Male SpragueDawley rats were uninephrectomized (UNX) or sham-operated at 3weeks of age and given either a normal-salt (NS) or high-salt (HS) diet. Effects on renal and cardiovascular functions were assessed in rats supplemented with substrate for NO synthase (L-Arg) or a superoxide dismutase mimetic (Tempol). Results Rats with UNX+HS developed hypertension and displayed increased renal NADPH oxidase activity, elevated levels of oxidative stress markers in plasma and urine, and reduced cGMP in plasma. Histological analysis showed signs of cardiac and renal inflammation and fibrosis. These changes were linked with abnormal renal autoregulation, measured as a stronger tubuloglomerular feedback (TGF) response. Simultaneous treatment with L-Arg or Tempol restored cGMP levels in plasma and increased markers of NO signalling in the kidney. This was associated with normalized TGF responses, attenuated hypertension and reduced signs of histopathological changes in the kidney and in the heart. Conclusion Reduction in nephron number during early life followed by chronic HS intake is associated with oxidative stress, impaired renal autoregulation and development of hypertension. Treatment strategies that increase NO bioavailability, or reduce levels of reactive oxygen species, were proven beneficial in this model of renal and cardiovascular disease.
9.	Wilkinson, Mark D., et al. (författare) Comment : The FAIR Guiding Principles for scientific data management and stewardship 2016 Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3 Tidskriftsartikel (refereegranskat)abstract There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders-representing academia, industry, funding agencies, and scholarly publishers-have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
10.	Yang, Ting, et al. (författare) Genetic Abrogation of Adenosine A(3) Receptor Prevents Uninephrectomy and High Salt-Induced Hypertension 2016 Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:7 Tidskriftsartikel (refereegranskat)abstract Background - Early-life reduction in nephron number (uninephrectomy [UNX]) and chronic high salt (HS) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating renal, cardiovascular, and metabolic functions as well as inflammatory processes; however, the specific role of the A(3) receptor in cardiovascular diseases is not clear. In this study, gene-modified mice were used to investigate the hypothesis that lack of A(3) signaling prevents the development of hypertension and attenuates renal and cardiovascular injuries following UNX in combination with HS (UNX-HS) in mice.Methods and Results - Wild-type (A(3)(+/+)) mice subjected to UNX-HS developed hypertension compared with controls (mean arterial pressure 106 +/- 3 versus 82 +/- 3 mm Hg; P<0.05) and displayed an impaired metabolic phenotype (eg, increased adiposity, reduced glucose tolerance, hyperinsulinemia). These changes were associated with both cardiac hypertrophy and fibrosis together with renal injuries and proteinuria. All of these pathological hallmarks were significantly attenuated in the A(3)(-/-) mice. Mechanistically, absence of A(3) receptors protected from UNX-HS-associated increase in renal NADPH oxidase activity and Nox2 expression. In addition, circulating cytokines including interleukins 1 beta, 6, 12, and 10 were increased in A(3)(+/+) following UNX-HS, but these cytokines were already elevated in naive A(3)(-/-) mice and did not change following UNX-HS.Conclusions - Reduction in nephron number combined with chronic HS intake is associated with oxidative stress, chronic inflammation, and development of hypertension in mice. Absence of adenosine A(3) receptor signaling was strongly protective in this novel mouse model of renal and cardiovascular disease.
11.	Brown, Russell, et al. (författare) Ischemic Preconditioning does not Protect against Renal Injury in Adenosine A1-receptor Knockout Mice Annan publikation (övrigt vetenskapligt/konstnärligt)
12.	Brown, Russell, 1966- (författare) The Influence of the Adenosine A1-receptor on Tubuloglomerular Feedback and Renin Release 2004 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The kidneys play a vital role in the maintenance of extracellular fluid and electrolyte balance and blood pressure. Adenosine, acting through the adenosine A1-receptor (A1R), and nitric oxide have been implicated in several of the regulatory mechanisms in the kidney. The A1R has been found to be present in the renal vasculature, primarily in the afferent arterioles, and in the proximal tubules. The tubuloglomerular feedback mechanism (TGF) is an important regulator of renal vascular tone and glomerular filtration rate. The aim of these investigations was to further elucidate the role of adenosine, acting through the A1R. Investigations on adenosine’s renal effects were performed on transgenic mice lacking the A1R.TGF response, elicited by increased distal salt load, was completely abolished in the A1R knockout (A1R -/- ) mice. Basal plasma-renin levels were found to be ~2-fold higher in the A1R -/- compared to the A1R wild-type (A1R+/+) mice. However, salt intake induced inverse changes in plasma-renin levels, indicating that adenosine tonically inhibits macula densa stimulated renin release. Anesthetized and conscious A1R -/- mice, measured telemetrically, had an increased blood pressure, which could be due to the increased plasma-renin levels. Despite the high plasma-renin levels, increased urinary sodium excretion was also observed in the A1R -/- animals. Ischemia caused a decrease in renal function in both A1R+/+ and A1R -/- mice. Ischemic preconditioning protected the A1R+/+ mice from subsequent ischemic episode but had no protective effect on the A1R -/- mice.Acute extracellular volume expansion greatly attenuates TGF sensitivity, thus facilitating the elimination of excess fluid. Acute inhibition of nNOS in volume-expanded rats was found to re-establish the attenuated TGF response caused by acute extracellular volume expansion.The results show that adenosine, acting through the A1R, plays an important role in mediating TGF response and consequently, regulating renin release, blood pressure, electrolyte balance and other vital renal mechanisms.
13.	Carlsson, Jörgen, et al. (författare) Planning for intracavitary anti-EGFR radionuclide therapy of gliomas : Literature review and data on EGFR expression 2006 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:1, s. 33-45 Tidskriftsartikel (refereegranskat)abstract Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.
14.	Carlström, Mattias, et al. (författare) Hydronephrosis causes salt-sensitive hypertension and impaired renal concentrating ability in mice 2007 Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:3, s. 293-301 Tidskriftsartikel (refereegranskat)abstract Aim: Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt-sensitive hypertension in rats. The mechanisms are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt-sensitive hypertension. Methods: PUUO was created in 3-week-old mice (C57bl/6J). Blood pressure and heart rate were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated. Results: All hydronephrotic animals developed salt-sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 ± 1 mmHg on normal salt diet to 120 ± 2 mmHg on high salt diet, compared with 103 ± 1 to 104 ± 1 in controls. Hydronephrotic animals showed increased diuresis and reduced ability to regulate electrolyte concentration. No differences in plasma renin concentration were found between the groups. The parenchymal weight and glomerular area of contralateral kidneys were significantly increased in the hydronephrotic animals. Histopathology of the hydronephrotic kidneys displayed areas with fibrosis, inflammation and glomerular changes. Conclusion: This study provides a model for PUUO in mice and demonstrates the presence of salt-sensitive hypertension and an impaired renal concentrating ability in mice which has not been described before.
15.	Carlström, Mattias, et al. (författare) Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals 2008 Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 294:2, s. 362-370 Tidskriftsartikel (refereegranskat)abstract Hydronephrotic animals develop renal injury and hypertension, which is associated with an abnormal tubuloglomerular feedback (TGF). The TGF sensitivity is coupled to nitric oxide (NO) in the macula densa. The involvement of reduced NO availability in the development of hypertension in hydronephrosis was investigated. Hydronephrosis was induced by ureteral obstruction in young rats. Blood pressure and renal excretion were measured in adulthood, under different sodium conditions, and before and after chronic administration of either N-G- nitro-L-arginine methyl ester (L-NAME) or L-arginine. Blood samples for ADMA, SDMA, and L-arginine analysis were taken and the renal tissue was used for histology and determination of NO synthase (NOS) proteins. TGF characteristics were determined by stop-flow pressure technique before and after administration of 7-nitroindazole (7-NI) or L-arginine. Hydronephrotic animals developed salt-sensitive hypertension, which was associated with pressure natriuresis and diuresis. The blood pressure response to L-NAME was attenuated and L-arginine supplementation decreased blood pressure in hydronephrotic animals, but not in the controls. Under control conditions, reactivity and sensitivity of the TGF response were greater in the hydronephrotic group. 7-NI administration increased TGF reactivity and sensitivity in control animals, whereas, in hydronephrotic animals, neuronal NOS (nNOS) inhibition had no effect. L-Arginine attenuated TGF response more in hydronephrotic kidneys than in controls. The hydronephrotic animals displayed various degrees of histopathological changes. ADMA and SDMA levels were higher and the renal expressions of nNOS and endothelial NOS proteins were lower in animals with hydronephrosis. Reduced NO availability in the diseased kidney in hydronephrosis, and subsequent resetting of the TGF mechanism, plays an important role in the development of hypertension.
16.	Carlström, Mattias, et al. (författare) SOD1-Deficiency Causes Salt-Sensitivity and Aggravates Hypertension in Hydronephrosis 2009 Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 297:1, s. R82-R92 Tidskriftsartikel (refereegranskat)abstract Background: Hydronephrosis causes renal dysfunction and salt-sensitive hypertension, which is associated with NO-deficiency and abnormal tubuloglomerular feedback (TGF) response. We investigated the role of oxidative stress for salt-sensitivity and for hypertension in hydronephrosis. Methods: Hydronephrosis was induced in SOD1-transgenic (SOD1-tg), SOD1-deficient (SOD1-ko) and wild-type mice and in rats. In mice, telemetric measurements were performed during normal (0.7% NaCl) and high sodium (4% NaCl) diets and with chronic Tempol supplementation. 8-iso-prostaglandin-F2alpha (F2-IsoPs) and protein excretion profiles and histology were investigated. The acute effects of Tempol on blood pressure and TGF were studied in rats. Results: In hydronephrosis, wild-type mice developed salt-sensitive hypertension (114+/-1 to 120+/-2 mmHg) which was augmented in SOD1-ko (125+/-3 to 135+/-4 mmHg), but abolished in SOD1-tg (109+/-3 to 108+/-3 mmHg). SOD1-ko controls displayed salt-sensitive blood pressure (108+/-1 to 115+/-2 mmHg), which was not found in wild-types or SOD1-tg. Chronic Tempol treatment reduced blood pressure in SOD1-ko controls (-7 mmHg) and in hydronephrotic wild-types (-8 mmHg) and SOD1-ko mice (-16 mmHg), but had no effect on blood pressure in wild-type or SOD1-tg controls. SOD1-ko controls and hydronephrotic wild-type and SOD1-ko mice exhibited increased fluid excretion associated with increased F2-IsoPs and protein excretion. The renal histopathological changes found in hydronephrotic wild-types were augmented in SOD1-ko and diminished in SOD-tg mice. Tempol attenuated blood pressure and normalized TGF response in hydronephrosis (DeltaPSF: 15.2+/-1.2 to 9.1+/-0.6 mmHg, TP: 14.3+/-0.8 to 19.7+/-1.4 nl/min). Conclusion: Oxidative stress due to SOD1-deficiency causes salt-sensitivity and plays a pivotal role for the development of hypertension in hydronephrosis. Increased superoxide formation may enhance TGF response and thereby contribute to hypertension.
17.	Duits, Flora H, et al. (författare) Performance and complications of lumbar puncture in memory clinics: Results of the multicenter lumbar puncture feasibility study. 2016 Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 12:2, s. 154-163 Tidskriftsartikel (refereegranskat)abstract Lumbar puncture (LP) is increasingly performed in memory clinics. We investigated patient-acceptance of LP, incidence of and risk factors for post-LP complications in memory clinic populations.
18.	Gao, Xiang, et al. (författare) Adenosine A(1)-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment 2011 Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 301:6, s. R1669-R1681 Tidskriftsartikel (refereegranskat)abstract Adenosine mediates tubuloglomerular feedback responses via activation of A(1)-receptors on the renal afferent arteriole. Increased preglomerular reactivity, due to reduced nitric oxide (NO) production or increased levels of ANG II and reactive oxygen species (ROS), has been linked to hypertension. Using A(1)-receptor knockout (A(1)(-/-)) and wild-type (A(1)(+/+)) mice we investigated the hypothesis that A(1)-receptors modulate arteriolar and blood pressure responses during NO synthase (NOS) inhibition or ANG II treatment. Blood pressure and renal afferent arteriolar responses were measured in nontreated mice and in mice with prolonged N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or ANG II treatment. The hypertensive responses to L-NAME and ANG II were clearly attenuated in A(1)(-/-) mice. Arteriolar contractions to L-NAME (10(-4) mol/l; 15 min) and cumulative ANG II application (10(-12) to 10(-6) mol/l) were lower in A(1)(-/-) mice. Simultaneous treatment with tempol (10(-4) mol/l; 15 min) attenuated arteriolar responses in A(1)(+/+) but not in A(1)(-/-) mice, suggesting differences in ROS formation. Chronic treatment with L-NAME or ANG II did not alter arteriolar responses in A(1)(-/-) mice, but enhanced maximal contractions in A(1)(+/+) mice. In addition, chronic treatments were associated with higher plasma levels of dimethylarginines (asymmetrical and symmetrical) and oxidative stress marker malondialdehyde in A(1)(+/+) mice, and gene expression analysis showed reduced upregulation of NOS-isoforms and greater upregulation of NADPH oxidases. In conclusion, adenosine A(1)-receptors enhance preglomerular responses during NO inhibition and ANG II treatment. Interruption of A(1)-receptor signaling blunts L-NAME and ANG II-induced hypertension and oxidative stress and is linked to reduced responsiveness of afferent arterioles.
19.	Gao, Xiang, et al. (författare) Extravasal albumin concentration modulates contractile responses of renal afferent arterioles 2018 Ingår i: Acta Physiologica. - : WILEY. - 1748-1708 .- 1748-1716. ; 222:2 Tidskriftsartikel (refereegranskat)abstract Aim: Afferent arterioles (AA) hold a key position in the regulation of renal blood flow and glomerular filtration rate. Being the effector site of tubuloglomerular feedback, the afferent arteriole contributes to the renal handling of sodium and fluid. Dehydration goes along with increased renal interstitial protein concentration. Here, the hypothesis was tested that extravasal protein concentration directly modulates afferent arteriolar tone, a mechanism which may contribute to body fluid volume control.Method: The effect of increased extravasal albumin concentration on the vascular reactivity was investigated in renal AA and interlobar arteries of mice, in rat renal AA and in pancreatic islet arterioles.Results: Albumin (2 and 4% in the bath solution) significantly potentiated the contractile response of renal afferent arterioles induced by angiotensin II and adenosine, as well as their combination, compared to the control situation (0.1% albumin). Albumin did not influence the contractility of larger renal vessels or pancreatic islet arterioles. Mimicking the increase in the osmolality induced by 4% albumin by applying mannitol to the bath solution also increased the response of renal arterioles to Ang II. However, the effect was smaller compared to that of albumin. The nitric oxide bioavailability, measured by DAF-FM fluorescence, was reduced in afferent arterioles exposed to 4% albumin.Conclusion: The protein-induced modulation of AA tone is mediated by the increased osmolality as well as by NO scavenging. The results suggest a possible contribution of these mechanisms to the control of extracellular fluid volume via adjustment of renal blood flow and glomerular filtration rate.
20.	Lai, En Yin, et al. (författare) Adenosine restores angiotensin II-induced contractions by receptor-independent enhancement of calcium sensitivity in renal arterioles 2006 Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 99:10, s. 1117-1124 Tidskriftsartikel (refereegranskat)abstract Adenosine is coupled to energy metabolism and regulates tissue blood flow by modulating vascular resistance. In this study, we investigated isolated, perfused afferent arterioles of mice, which were subjected to desensitization during repeated applications of angiotensin II. Exogenously applied adenosine restores angiotensin II-induced contractions by increasing calcium sensitivity of the arterioles, along with augmented phosphorylation of the regulatory unit of the myosin light chain. Adenosine restores angiotensin II-induced contractions via intracellular action, because inhibition of adenosine receptors do not prevent restoration, but inhibition of NBTI sensitive adenosine transporters does. Restoration was prevented by inhibition of Rho-kinase, protein kinase C, and the p38 mitogen-activated protein kinase, which modulate myosin light chain phosphorylation and thus calcium sensitivity in the smooth muscle. Furthermore, adenosine application increased the intracellular ATP concentration in LuciHEK cells. The results of the study suggest that restoration of the angiotensin II-induced contraction by adenosine is attributable to the increase of the calcium sensitivity by phosphorylation of the myosin light chain. This can be an important component of vascular control during ischemic and hypoxic conditions. Additionally, this mechanism may contribute to the mediation of the tubuloglomerular feedback by adenosine in the juxtaglomerular apparatus of the kidney.
21.	Lai, En Yin, et al. (författare) Contribution of adenosine receptors in the control of arteriolar tone and adenosine-angiotensin II interaction 2006 Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 70:4, s. 690-698 Tidskriftsartikel (refereegranskat)abstract Adenosine (Ado) mediates vasoconstriction via A(1)-Ado receptors and vasodilation via A(2)-Ado receptors in the kidney. It interacts with angiotensin II (Ang II), which is important for renal hemodynamics and tubuloglomerular feedback (TGF). The aim was to investigate the function of Ado receptors in the Ado -Ang II interaction in mouse microperfused, afferent arterioles. Ado (10(-11)-10(-4) mol/l) caused a biphasic response: arteriolar diameters were reduced (-7%) at Ado 10(-11)-10(-9) mol/l and returned to control values at higher concentrations. Treatment with Ang II (10(-10) mol/l) transformed the response into a concentration-dependent constriction. N-6-cyclopentyladenosine (A(1)-Ado receptor agonist) reduced diameters (12% at 10(-6) mol/l). Application of CGS21680 (10(-12)-10(-4) mol/l, A(2A) receptor agonist) increased the diameter by 13%. Pretreatment with ZM241385 (A(2A)-Ado receptor antagonist) alone or in combination with MRS1706 (A(2B)-Ado receptor antagonist) resulted in a pure constriction upon Ado, whereas 8-cyclopentyltheophylline (CPT) (A(1)-Ado receptor antagonist) inhibited the constrictor response. Afferent arterioles of mice lacking A(1)-Ado receptor did not show constriction upon Ado. Treatment with Ado (10(-8) mol/l) increased the response upon Ang II, which was blocked by CPT. Ado (10(-5) mol/l) did not influence the Ang II response, but an additional blockade of A(2)-Ado receptors enhanced it. The action of Ado on constrictor A(1)-Ado receptors and dilatory A(2)-Ado receptors modulates the interaction with Ang II. Both directions of Ado-Ang II interaction, which predominantly leads to an amplification of the contractile response, are important for the operation of the TGF.
22.	Lai, En Yin, et al. (författare) Norepinephrine increases calcium sensitivity of mouse afferent arteriole, thereby enhancing angiotensin II-mediated vasoconstriction 2009 Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 76:9, s. 953-959 Tidskriftsartikel (refereegranskat)abstract Many agents constrict isolated afferent arterioles only at concentrations higher than their physiological levels. Here we determined if norepinephrine, as released by sympathetic nerve activity, could influence the angiotensin II responsiveness of isolated mouse afferent arterioles. Pretreatment of the arterioles for short periods with norepinephrine significantly increased the ability of 10 picomolar angiotensin II to constrict the vessels, an effect inhibited by the alpha receptor blockers prazosin (alpha-1) or yohimbine (alpha-2). Although the intracellular calcium transients induced by angiotensin were not different, phosphorylation of the 20 kDa myosin light chain was significantly increased in the presence of norepinephrine. Phosphorylation of the p38 mitogen-activated protein kinase was not changed. Phosphorylation of the myosin phosphatase targeting subunit at Thr696, but not at Thr850, was significantly enhanced by, norepinephrine pretreatment, thus increasing the calcium sensitivity of the arteriolar smooth muscle. Our results show that norepinephrine increases afferent arteriolar sensitivity to angiotensin II by means of alpha receptor activation, causing increased calcium sensitivity through phosphorylation of the myosin phosphatase targeting subunit. Kidney International (2009) 76, 953-959; doi:10.1038/ki.2009.261; published online 22 July 2009
23.	Patzak, Andreas, et al. (författare) Adenosine enhances long term the contractile response to angiotensin II in afferent arterioles 2007 Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 293:6, s. R2232-R2242 Tidskriftsartikel (refereegranskat)abstract Adenosine (Ado) enhances ANG II-induced constrictions of afferent arterioles (Af) by receptor-dependent and -independent pathways. Here, we test the hypothesis that transient Ado treatment has a sustained effect on Af contractility, resulting in increased ANG II responses after longer absence of Ado. Treatment with Ado (cumulative from 10(-11) to 10(-4) mol/l) and consecutive washout for 10 or 30 min increased constrictions on ANG II in isolated, perfused Af. Cytosolic calcium transients on ANG II were not enhanced in Ado-treated vessels. Selective or global inhibition of A(1)- and A(2)-adenosine receptors did not inhibit the Ado effect. Nitrobenzylthioinosine (an Ado transport inhibitor) clearly reduced the Ado-mediated responses. Selective inhibition of p38 MAPK with SB-203580 also prevented the Ado effect. Inosine treatment did not influence arteriolar reactivity to ANG II. Contractile responses of Af on norepinephrine and endothelin-1 were not influenced by Ado. Phosphorylation of the p38 MAPK and of the regulatory unit of 20-kDa myosin light chain was enhanced after Ado treatment and ANG II in Af. However, phosphorylation of p38 MAPK induced by norepinephrine or endothelin-1 was reduced in vessels treated with Ado, whereas 20-kDa myosin light chain was unchanged. The results suggest an intracellular, long-lasting mechanism including p38 MAPK activation responsible for the increase of ANG II-induced contractions by Ado. The effect is not calcium dependent and specific for ANG II. The prolonged enhancement of the ANG II sensitivity of Af may be important for tubuloglomerular feedback.
24.	Patzak, Andreas, et al. (författare) Angiotensin II-nitric oxide interaction in glomerular arterioles. 2005 Ingår i: Clin Exp Pharmacol Physiol. - 0305-1870. ; 32:5-6, s. 410-4 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
25.	Peleli, Maria, et al. (författare) Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis 2016 Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 310:1, s. F43-F56 Tidskriftsartikel (refereegranskat)abstract Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal excretion pattern, NOX activity and expression, as well as components of RAAS were characterized. On normal salt diet, PUUO rats had elevated blood pressure compared with controls (115±3 vs 87±1 mmHg), and displayed increased urine production and lower urine osmolality. Blood pressure change in response to salt loading (salt-sensitivity) was more pronounced in the PUUO group compared with controls (15±2 vs 5±1mmHg). Renal denervation in PUUO rats attenuated hypertension (97±3mmHg) and salt-sensitivity (5±1mmHg), and normalized renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression, as well as renin and AT1A receptor expression, were increased in renal cortex from PUUO rats, and normalized by denervation. Plasma sodium and potassium levels were elevated in PUUO rats and normalized after renal denervation. Denervation in PUUO rats was also associated with reduced NOX expression, superoxide production and fibrosis in the heart. This study emphasizes a link between renal nerves, NOX function, and development of hypertension.
26.	Porpino, Suenia K. P., et al. (författare) Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II-mediated hypertension 2016 Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 173:14, s. 2290-2302 Tidskriftsartikel (refereegranskat)abstract Background and PurposeNO deficiency and oxidative stress are crucially involved in the development or progression of cardiovascular disease, including hypertension and stroke. We have previously demonstrated that acute treatment with the newly discovered organic nitrate, 2-nitrate-1,3-dibuthoxypropan (NDBP), is associated with NO-like effects in the vasculature. This study aimed to further characterize the mechanism(s) and to elucidate the therapeutic potential in a model of hypertension and oxidative stress. Experimental ApproachA combination of ex vivo, in vitro and in vivo approaches was used to assess the effects of NDBP on vascular reactivity, NO release, NADPH oxidase activity and in a model of hypertension. Key ResultsEx vivo vascular studies demonstrated NDBP-mediated vasorelaxation in mesenteric resistance arteries, which was devoid of tolerance. In vitro studies using liver and kidney homogenates revealed dose-dependent and sustained NO generation by NDBP, which was attenuated by the xanthine oxidase inhibitor febuxostat. In addition, NDBP reduced NADPH oxidase activity in the liver and prevented angiotensin II-induced activation of NADPH oxidase in the kidney. In vivo studies showed that NDBP halted the progression of hypertension in mice with chronic angiotensin II infusion. This was associated with attenuated cardiac hypertrophy, and reduced NADPH oxidase-derived oxidative stress and fibrosis in the kidney and heart. Conclusion and ImplicationsThe novel organic nitrate NDBP halts the progression of angiotensin II-mediated hypertension. Mechanistically, our findings suggest that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase.
27.	Sudireddy, B. R., et al. (författare) Development of Robust Metal-Supported SOFCs and Stack Components in EU METSAPP Consortium 2017 Ingår i: Fuel Cells. - : Wiley. - 1615-6846 .- 1615-6854. ; 17:4, s. 508-516 Tidskriftsartikel (refereegranskat)abstract The potential of MS-SOFCs was demonstrated through the previous EU METSOFC project, which concluded that the development of oxidation resistant novel metal-supported solid oxide fule cell (MS-SOFC) design and stack is the requirement to advance this technology to the next level. The following EU METSAPP project has been executed with an overall aim of developing advanced metal-supported cells and stacks based on a robust, reliable and up-scalable technology. During the project, oxidation resistant nanostructured anodes based on modified SrTiO3 were developed and integrated into MS-SOFCs to enhance their robustness. In addition, the manufacturing of metal-supported cells with different geometries, scalability of the manufacturing process was demonstrated and more than 200 cells with an area of approximate to 150 cm(2) were produced. The electrochemical performance of different cell generations was evaluated and best performance and stability combination was observed with doped SrTiO3 based anode designs. Furthermore, numerical models to understand the corrosion behavior of the MS-SOFCs were developed and validated. Finally, the cost effective concept of coated metal interconnects was developed, which resulted in 90% reduction in Cr evaporation, three times lower Cr2O3 scale thickness and increased lifetime. The possibility of assembling these cells into two radically different stack designs was demonstrated.
28.	Sällström, Johan, et al. (författare) Impaired EphA4 signaling leads to congenital hydronephrosis, renal injury, and hypertension 2013 Ingår i: AM J PHYSIOL-RENAL. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 305:1, s. F71-F79 Tidskriftsartikel (refereegranskat)abstract Experimental hydronephrosis induced by partial ureteral obstruction at 3 wk of age causes hypertension and renal impairment in adult rats and mice. Signaling by Ephrin receptors (Eph) and their ligands (ephrins) importantly regulates embryonic development. Genetically modified mice, where the cytoplasmic domain of the EphA4 receptor has been substituted by enhanced green fluorescent protein (EphA4(gf/gf)), develop spontaneous hydronephrosis and provide a model for further studies of the disorder. The present study aimed to determine if animals with congenital hydronephrosis develop hypertension and renal injuries, similar to that of experimental hydronephrosis. Ultrasound and Doppler techniques were used to visualize renal impairment in the adult mice. Telemetric blood pressure measurements were performed in EphA4(gf/gf) mice and littermate controls (EphA4(+/+)) during normal (0.7% NaCl)- and high (4% NaCl)-sodium conditions. Renal excretion, renal plasma flow, and glomerular filtration were studied, and histology and morphology of the kidneys and ureters were performed. EphA4(gf/gf) mice developed variable degrees of hydronephrosis that correlated with their blood pressure level. In contrast to EphA4(+/+), the EphA4(gf/gf) mice displayed salt-sensitive hypertension, reduced urine concentrating ability, reduced renal plasma flow, and lower glomerular filtration rate. Kidneys from EphA4(gf/gf) mice showed increased renal injuries, as evidenced by fibrosis, inflammation, and glomerular and tubular changes. In conclusion, congenital hydronephrosis causes hypertension and renal damage, similar to that observed in experimentally induced hydronephrosis. This study further reinforces the supposed causal link between hydronephrosis and later development of hypertension in humans.
29.	Wu, D., et al. (författare) A novel strained Si0.7Ge0.3 surface-channel pMOSFET with an ALD TiN/Al2O3/HfAlOx/Al2O3 gate stack 2003 Ingår i: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 24:3, s. 171-173 Tidskriftsartikel (refereegranskat)abstract Proof-of-concept pMOSFETs with a strained-Si0.7Ge0.3 surface-channel deposited by selective epitaxy and a TiN/Al2O3/HfAIO(x)/Al2O3 gate stack grown by atomic layer chemical vapor deposition (ALD) techniques were fabricated. The Si0.7Ge0.3 pMOSFETs exhibited more than 30% higher current drive and peak transconductance than reference Si pMOSFETs with the same gate stack. The effective mobility for the Si reference coincided with the universal hole mobility curve for Si. The presence of a relatively low density of interface states, determined as 3.3x10(11) cm(-2) eV(-1), yielded a subthreshold slope of 75 mV/dec. for the Si reference. For the Si0.7Ge0.3 pMOSFETs, these values were 1.6x10(12) cm(-2) eV(-1) and 110 mV/dec., respectively.
30.	Xu, Nan, et al. (författare) Reactive oxygen species in renal vascular function 2020 Ingår i: Acta Physiologica. - : WILEY. - 1748-1708 .- 1748-1716. ; 229:4 Forskningsöversikt (refereegranskat)abstract Reactive oxygen species (ROS) are produced by the aerobic metabolism. The imbalance between production of ROS and antioxidant defence in any cell compartment is associated with cell damage and may play an important role in the pathogenesis of renal disease. NADPH oxidase (NOX) family is the major ROS source in the vasculature and modulates renal perfusion. Upregulation of Ang II and adenosine activates NOX via AT1R and A1R in renal microvessels, leading to superoxide production. Oxidative stress in the kidney prompts renal vascular remodelling and increases preglomerular resistance. These are key elements in hypertension, acute and chronic kidney injury, as well as diabetic nephropathy. Renal afferent arterioles (Af), the primary resistance vessel in the kidney, fine tune renal hemodynamics and impact on blood pressure. Vice versa, ROS increase hypertension and diabetes, resulting in upregulation of Af vasoconstriction, enhancement of myogenic responses and change of tubuloglomerular feedback (TGF), which further promotes hypertension and diabetic nephropathy. In the following, we highlight oxidative stress in the function and dysfunction of renal hemodynamics. The renal microcirculatory alterations brought about by ROS importantly contribute to the pathophysiology of kidney injury, hypertension and diabetes.
31.	Al-Mashhadi, Ammar, et al. (författare) Changes of arterial pressure following relief of obstruction in adults with hydronephrosis 2018 Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 123:4, s. 216-224 Tidskriftsartikel (refereegranskat)abstract Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.
32.	Al-Mashhadi, Ammar Nadhom Farman, et al. (författare) Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children 2018 Ingår i: Pediatric nephrology (Berlin, West). - : Springer. - 0931-041X .- 1432-198X. ; 33:4, s. 639-649 Tidskriftsartikel (refereegranskat)abstract Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction
33.	Al-Mashhadi, Ammar Nadhom Farman, et al. (författare) Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis 2015 Ingår i: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131 .- 1873-4898. ; 11:2, s. 91.e1-91.e6 Tidskriftsartikel (refereegranskat)abstract Objective Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Patients and methods Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. Results As shown in the summary figure, postoperative systolic (103 +/- 2 mmHg) and diastolic (62 +/- 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 +/- 4 and 69 +/- 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Discussion Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. Conclusion This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.
34.	Brown, Russell D, et al. (författare) Influence of the adenosine A1 receptor on blood pressure regulation and renin release. 2006 Ingår i: Am J Physiol Regul Integr Comp Physiol. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 290:5, s. R1324-9 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
35.	Brown, Russell D., et al. (författare) Tubuloglomerular feedback response in the prenatal and postnatal ovine kidney 2011 Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 300:6, s. F1368-F1374 Tidskriftsartikel (refereegranskat)abstract Brown RD, Turner AJ, Carlstrom M, Persson AE, Gibson KJ. Tubuloglomerular feedback response in the prenatal and postnatal ovine kidney. Am J Physiol Renal Physiol 300: F1368-F1374, 2011. First published March 30, 2011; doi:10.1152/ajprenal. 00019.2011.-The tubuloglomerular feedback mechanism (TGF) plays an important role in regulating single-nephron glomerular filtration rate (GFR) by coupling distal tubular flow to arteriolar tone. It is not known whether TGF is active in the developing kidney or whether it can regulate renal vascular tone and thus GFR during intrauterine life. TGF characteristics were examined in late-gestation ovine fetuses and lambs under normovolemic and volume-expanded (VE) conditions. Lambs and pregnant ewes were anesthetized and the fetuses were delivered via a caesarean incision into a heated water bath, with the umbilical cord intact. Under normovolemic conditions, mean arterial pressure of the fetuses was lower than lambs (51 +/- 1 vs. 64 +/- 3 mmHg). The maximum TGF response (Delta P(SFmax)) was found to be lower in fetuses than lambs when tubular perfusion was increased from 0 to 40 nl/min (5.4 +/- 0.7 vs. 10.6 +/- 0.4 mmHg). Furthermore, the flow rate eliciting half-maximal response [turning point (TP)] was 15.7 +/- 0.9 nl/min in fetuses compared with 19.3 +/- 1.0 nl/min in lambs, indicating a greater TGF sensitivity of the prenatal kidney. VE decreased Delta P(SFmax) (4.2 +/- 0.4 mmHg) and increased TP to 23.7 +/- 1.3 nl/min in lambs. In fetuses, VE increased stop-flow pressure from 26.6 +/- 1.5 to 30.3 +/- 0.8 mmHg, and reset TGF sensitivity so that TP increased to 21.3 +/- 0.7 nl/min, but it had no effect on Delta P(SFmax). This study provides direct evidence that the TGF mechanism is active during fetal life and responds to physiological stimuli. Moreover, reductions in TGF sensitivity may contribute to the increase in GFR at birth.
36.	Brown, Russell, et al. (författare) Neuronal Nitric Oxide Synthase Inhibition Sensitizes the Tubuloglomerular Feedback Mechanism after Volume Expansion 2004 Ingår i: Kidney Int. ; 65, s. 1349-56 Tidskriftsartikel (refereegranskat)
37.	Brown, Russell, et al. (författare) The Influence of the Adenosine A1-receptor on Blood Pressure Regulation and Renin Release Annan publikation (övrigt vetenskapligt/konstnärligt)
38.	Carlström, Mattias, et al. (författare) Angiogenesis inhibition causes hypertension and placental dysfunction in a rat model of preeclampsia 2009 Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 27:4, s. 829-837 Tidskriftsartikel (refereegranskat)abstract Background Preeclampsia is a serious pregnancy complication, accompanied by increased maternal and fetal morbidity. Different models have been used to study preeclampsia, but none of these display all the key features of the disease. Method We investigated the effects on maternal blood pressure and fetal outcome exerted by the angiogenesis inhibitor Suramin (1100 mg/kg i.p.) during early placentation. Blood pressure and heart rate were measured continuously with telemetry in Sprague - Dawley rats of four experimental groups: nonpregnant controls, Suramin-treated nonpregnant rats, pregnant controls and pregnant Suramin-treated rats. Blood samples were collected before pregnancy and at gestational day 20 for analysis of renin and sFIt-1. The fetal and placental morphology were evaluated after caesarian section on gestational day 20. Results The blood pressure of the pregnant Suramin-treated rats successively increased during pregnancy and differed by 17 mmHg at gestational day 20 compared with the pregnant control rats. In the pregnant Suramin-treated rats group, the renin levels increased (+122%) and the sFIt-1 levels decreased (-58%) during pregnancy. The pregnant Suramin-treated fetuses and placentae were smaller (2.8 g and 0.51 g) than the pregnant controls rats' fetuses and placentae (3.5g and 0.56g). Resorptions tended to be higher in the pregnant Suramin-treated rat litters compared with the pregnant control rat litters (P = 0.08). The area of the maternal blood vessels in the mesometrial triangle was smaller in the pregnant Suramin-treated rats group than in the pregnant control rats group. Conclusion The inhibition of uterine angiogenesis increases maternal blood pressure and compromises fetal and placental development. Placental hypoxia and subsequent activation of the renin-angiotensin system may play an important role for the hypertension. J Hypertens 27:829-837 (C) 2009 Wolters Kluwer Health \| Lippincott Williams & Wilkins.
39.	Carlström, Mattias, et al. (författare) Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis 2015 Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 23:4, s. 295-306 Tidskriftsartikel (refereegranskat)abstract Aims: Inorganic nitrate and nitrite from endogenous and dietary sources have emerged as alternative substrates for nitric oxide (NO) formation in addition to the classic L-arginine NO synthase (NOS)-dependent pathway. Here, we investigated a potential cross-talk between these two pathways in the regulation of vascular function. Results: Long-term dietary supplementation with sodium nitrate (0.1 and 1mmol kg(-1) day(-1)) in rats caused a reversible dose-dependent reduction in phosphorylated endothelial NOS (eNOS) (Ser1177) in aorta and a concomitant increase in phosphorylation at Thr495. Moreover, eNOS-dependent vascular responses were attenuated in vessels harvested from nitrate-treated mice or when nitrite was acutely added to control vessels. The citrulline-to-arginine ratio in plasma, as a measure of eNOS activity, was reduced in nitrate-treated rodents. Telemetry measurements revealed that a low dietary nitrate dose reduced blood pressure, whereas a higher dose was associated with a paradoxical elevation. Finally, plasma cyclic guanosine monophosphate increased in mice that were treated with a low dietary nitrate dose and decreased with a higher dose. Innovation and Conclusions: These results demonstrate the existence of a cross-talk between the nitrate-nitrite-NO pathway and the NOS-dependent pathway in control of vascular NO homeostasis. Antioxid. Redox Signal. 23, 295-306.
40.	Carlström, Mattias, et al. (författare) Hydronephrosis causes salt-sensitive hypertension in rats 2006 Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 24:7, s. 1437-1443 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Hypertension is a common disease in the Western world and approximately 5% of all cases are secondary to kidney malfunction. It is not clear whether unilateral hydronephrosis due to partial obstruction affects blood pressure. AIM: The aim of this study was to determine whether hypertension develops and to investigate the effects of different salt diets on the blood pressure in hydronephrotic animals. METHODS: Unilateral partial ureteral obstruction was created in 3-week-old Sprague-Dawley rats. A telemetric device was implanted 4-6 weeks later and blood pressure was measured on normal, low- and high-salt diets. Plasma samples were collected on all diets for renin analysis. RESULTS: All hydronephrotic animals developed hypertension that correlated to the degree of hydronephrosis. The blood pressure increased slowly with time and was salt sensitive. In severe hydronephrosis, blood pressure increased from 118 ± 5 mmHg on low salt to 140 ± 6 mmHg on high salt intake, compared to control levels of 82 ± 2 and 84 ± 2 mmHg, respectively. Plasma renin concentration was increased in the hydronephrotic group of animals compared to controls on all diets, but the difference was only significant on a normal salt diet, 165 ± 15 versus 86 ± 12 μGU/ml respectively. In animals with severe hydronephrosis the plasma renin levels were lower, and the changes less, than in those with mild and moderate hydronephrosis. CONCLUSION: This study demonstrates the presence of a salt-sensitive hypertension in hydronephrosis. A systemic effect of the renin-angiotensin system alone cannot be responsible for the hypertension.
41.	Carlström, Mattias, et al. (författare) Important role of NAD(P)H oxidase 2 in the regulation of the tubuloglomerular feedback 2009 Ingår i: Hypertension. - : American Heart Association, Inc.. - 0194-911X .- 1524-4563. ; 53:3, s. 456-457 Tidskriftsartikel (refereegranskat)
42.	Carlström, Mattias, et al. (författare) Nitric oxide deficiency and increased adenosine response of afferent arterioles in hydronephrotic mice with hypertension 2008 Ingår i: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 51:5, s. 1386-1392 Forskningsöversikt (refereegranskat)abstract Afferent arterioles were used to investigate the role of adenosine, angiotensin II, NO, and reactive oxygen species in the pathogenesis of increased tubuloglomerular feedback response in hydronephrosis. Hydronephrosis was induced in wild-type mice, superoxide dismutase-1 overexpressed mice (superoxide-dismutase-1 transgenic), and deficient mice (superoxide dismutase-1 knockout). Isotonic contractions in isolated perfused arterioles and mRNA expression of NO synthase isoforms, adenosine, and angiotensin II receptors were measured. In wild-type mice, N(G)-nitro-L-arginine methyl ester (L-NAME) did not change the basal arteriolar diameter of hydronephrotic kidneys (-6%) but reduced it in control (-12%) and contralateral arterioles (-43%). Angiotensin II mediated a weaker maximum contraction of hydronephrotic arterioles (-18%) than in control (-42%) and contralateral arterioles (-49%). The maximum adenosine-induced constriction was stronger in hydronephrotic (-19%) compared with control (-8%) and contralateral kidneys (+/-0%). The response to angiotensin II became stronger in the presence of adenosine in hydronephrotic kidneys and attenuated in contralateral arterioles. L-NAME increased angiotensin II responses of all of the groups but less in hydronephrotic kidneys. The mRNA expression of endothelial NO synthase and inducible NO synthase was upregulated in the hydronephrotic arterioles. No differences were found for adenosine or angiotensin II receptors. In superoxide dismutase-1 transgenic mice, strong but similar L-NAME response (-40%) was observed for all of the groups. This response was totally abolished in arterioles of hydronephrotic superoxide dismutase-1 knockout mice. In conclusion, hydronephrosis is associated with changes in the arteriolar reactivity of both hydronephrotic and contralateral kidneys. Increased oxidative stress, reduced NO availability, and stronger reactivity to adenosine of the hydronephrotic kidney may contribute to the enhanced tubuloglomerular feedback responsiveness in hydronephrosis and be involved in the development of hypertension.
43.	Carlström, Mattias, et al. (författare) Relief of chronic partial ureteral obstruction attenuates salt-sensitive hypertension in rats 2007 Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:1, s. 67-75 Tidskriftsartikel (refereegranskat)abstract Aim: The incidence of hydronephrosis due to ureteropelvic junction obstruction is approx. 0.5%. During the last decade, the management of non-symptomatic hydronephrosis has become much more conservative, but the long-term physiological consequences of this policy are not clear. Previously, we have shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. Methods: Partial unilateral ureteral obstruction was created in 3-week-old male Sprague–Dawley rats and blood pressure was measured telemetrically 4–6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral nephrectomy. Results: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 ± 15 μGU mL−1 vs. 96 ± 12 μGU mL−1, respectively), but after the ipsilateral nephrectomy no differences were found between the groups. In the hydronephrotic animals both ipsilateral nephrectomy and ureterovesicostomy reduced the blood pressure and salt-sensitivity but the former still differed significantly from the controls. In contralaterally, nephrectomized hydronephrotic animals the salt-sensitive hypertension became more pronounced. Conclusion: Hydronephrosis in rats causes salt-sensitive hypertension that can be markedly reduced by removing the hydronephrotic kidney or relieving the obstruction by ureterovesicostomy. The mechanisms appear to be intrarenal and primarily located in the diseased kidney, but a secondary mechanism is also present.
44.	Carlström, Mattias, et al. (författare) Role of NOX2 in the regulation of afferent arteriole responsiveness 2009 Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 296:1, s. R72-R79 Tidskriftsartikel (refereegranskat)abstract NADPH oxidases (NOX) are the major source of reactive oxygen species (ROS) in the vasculature and contribute to the control of renal perfusion. The role of NOX2 in the regulation of blood pressure and afferent arteriole responsiveness was investigated in NOX2(-/-) and wild-type mice. Arteriole constrictions to ANG II (10(-14)-10(-6) mol/l) were weaker in NOX2(-/-) compared with wild types. N(omega)-nitro-l-arginine methyl ester (l-NAME; 10(-4) mol/l) treatment reduced basal diameters significantly more in NOX2(-/-) (-18%) than in wild types (-6%) and augmented ANG II responses. Adenosine (10(-11)-10(-4) mol/l) constricted arterioles of wild types but not of NOX2(-/-). However, simultaneous inhibition of adenosine type-2 receptors induced vasoconstriction, which was stronger in NOX2(-/-). Adenosine (10(-8) mol/l) enhanced the ANG II response in wild type, but not in NOX2(-/-). This sensitizing effect by adenosine was abolished by apocynin. Chronic ANG II pretreatment (14 days) did not change the ANG II responses in NOX2(-/-), but strengthened the response in wild types. ANG II pretreatment augmented the l-NAME response in NOX2(-/-) (-33%), but not in wild types. Simultaneous application of l-NAME and ANG II caused a stronger constriction in the NOX2(-/-) (-64%) than in wild types (-46%). Basal blood pressures were similar in both genotypes, however, chronic ANG II infusion elevated blood pressure to a greater extent in wild-type (15 +/- 1%) than in NOX2(-/-) (8 +/- 1%) mice. In conclusion, NOX2 plays an important role in the control of afferent arteriole tone and is involved in the contractile responses to ANG II and/or adenosine. NOX2 can be activated by elevated ANG II and may play an important role in ANG II-induced hypertension. NOX2-derived ROS scavenges nitric oxide, causing subsequent nitric oxide-deficiency.
45.	Carlström, Mattias, et al. (författare) Superoxide Dismutase 1 Limits Renal Microvascular Remodeling and Attenuates Arteriole and Blood Pressure Responses to Angiotensin II via Modulation of Nitric Oxide Bioavailability 2010 Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 56:5, s. 907-913 Tidskriftsartikel (refereegranskat)abstract Oxidative stress is associated with vascular remodeling and increased preglomerular resistance that are both implicated in the pathogenesis of renal and cardiovascular disease. Angiotensin II induces superoxide production, which is metabolized by superoxide dismutase (SOD) or scavenged by NO. We investigated the hypothesis that SOD1 regulates renal microvascular remodeling, blood pressure, and arteriolar responsiveness and sensitivity to angiotensin II using SOD1-transgenic (SOD1-tg) and SOD1-knockout (SOD1-ko) mice. Blood pressure, measured telemetrically, rose more abruptly during prolonged angiotensin II infusion in SOD1-ko mice. The afferent arteriole media: lumen ratios were reduced in SOD1-tg and increased in SOD1-ko mice. Afferent arterioles from nontreated wild types had graded contraction to angiotensin II (sensitivity: 10(-9) mol/L; responsiveness: 40%). Angiotensin II contractions were less sensitive (10(-8) mol/L) and responsive (14%) in SOD1-tg but more sensitive (10(-13) mol/L) and responsive (89%) in SOD1-ko mice. Arterioles from SOD1-ko had 4-fold increased superoxide formation with angiotensin II at 10(-9) mol/L. N-G-nitro-L-arginine methyl ester reduced arteriole diameter of SOD1-tg and enhanced angiotensin II sensitivity and responsiveness of wild-type and SOD1-tg mice to the level of SOD1-ko mice. SOD mimetic treatment with Tempol increased arteriole diameter and normalized the enhanced sensitivity and responsiveness to angiotensin II of SOD1-ko mice but did not affect wild-type or SOD1-tg mice. Neither SOD1 deficiency nor overexpression was associated with changes in nitrate/nitrite excretion or renal mRNA expression of NO synthase, NADPH oxidase, or SOD2/SOD3 isoforms and angiotensin II receptors. In conclusion, SOD1 limits afferent arteriole remodeling and reduces sensitivity and responsiveness to angiotensin II by reducing superoxide and maintaining NO bioavailability. This may prevent an early and exaggerated blood pressure response to angiotensin II.
46.	Chechkin, G.A., et al. (författare) On spectrum of the Laplacian in a circle perforated along the boundary : application to a Friedrichs-type inequality 2011 Rapport (övrigt vetenskapligt/konstnärligt)
47.	Chechkin, G.A., et al. (författare) On the Friedrichs inequality in a domain perforated aperiodically along the boundary : Homogenization procedure. Asymptotics for parabolic problems 2009 Ingår i: Russian journal of mathematical physics. - 1061-9208 .- 1555-6638. ; 16:1, s. 1-16 Tidskriftsartikel (refereegranskat)abstract This paper is devoted to the asymptotic analysis of functions depending on a small parameter characterizing the microinhomogeneous structure of the domain on which the functions are defined. We derive the Friedrichs inequality for these functions and prove the convergence of solutions to corresponding problems posed in a domain perforated aperiodically along the boundary. Moreover, we use numerical simulation to illustrate the results.
48.	Chechkin, G. A., et al. (författare) On the precise asymptotics of the constant in Friedrich's inequality for functions vanishing on the part of the boundary with microinhomogeneous structure 2007 Ingår i: Journal of inequalities and applications. - : Springer Science and Business Media LLC. - 1025-5834 .- 1029-242X. Tidskriftsartikel (refereegranskat)abstract We construct the asymptotics of the sharp constant in the Friedrich-type inequality for functions, which vanish on the small part of the boundary Γ1ɛ. It is assumed that Γ1ɛ consists of (1/δ)n-1 pieces with diameter of order O(ɛδ). In addition, δ=δ(ɛ) and δ→0 as ɛ→0.
49.	Clausen, Torben, et al. (författare) Jens Christian Skou awarded the Nobel prize in chemistry for the identification of the Na+, K(+)-pump 1998 Ingår i: Acta Physiol. Scand.. ; 163, s. 1- Tidskriftsartikel (refereegranskat)
50.	Gao, Xiang, et al. (författare) Important role of P2Y receptors for islet blood flow regulation in anesthetized rats during acute and chronic hyperglycemia Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Pancreatic islet blood flow is regulated through a complex interplay between nervous, metabolic and local endothelial factors. We have previously shown that adenosine is an important vasodilator in the metabolic regulation of islet blood flow and now wanted to examine whether also ATP/ADP/AMP could affect islet blood perfusion through P2Y receptors. To achieve this we examined local blood flow values in normoglycemic and acutely hyperglycemic Sprague-Dawley rats as well as GK rats, a type 2 diabetes model. We inhibited P2Y receptors in general with suramine and, since P2Y13 receptors are known to inhibit insulin secretion, we also examined the effects of a selective P2Y13 receptor inhibitor, viz. MRS2211. We found that all GK rats were hyperglycemic and hypertensive when compared to SD rats. Basal islet blood flow in SD rats was decreased by MRS2211, and there was a trend for this to occur also after suramine administration. The glucose-induced islet blood flow increase in SD rats was impaired after suramine and MRS2211 treatment. GK rats had higher islet blood flow, but not islet vascular conductance, than SD rats, which did not react to acute hyperglycemia or the P2Y receptor inhibitors. Similar findings were made in an islet arteriole perfusion model, suggesting that local P2Y receptors are involved. A surprising finding was that especially suramine markedly increased colonic blood flow in SD rats, and decreased this blood flow in GK rats. We conclude that not only adenosine, but also also ATP and especially ADP stimulate both basal and glucose-stimulated islet blood flow in anesthetized SD rats, but this response is not seen in GK rats. Also colonic blood flow seems to be sensitive to P2Y receptors and increase its blood flow when these receptors are inhibited. The mechanisms behind this are unknown.

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