1. |
- Berglund, Felix, et al.
(author)
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Acute and long-term renal effects after iodine contrast media-enhanced computerised tomography in the critically ill-a retrospective bi-centre cohort study.
- 2024
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In: European Radiology. - 0938-7994 .- 1432-1084. ; 34:3, s. 1736-1745
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine if current clinical use of iodine contrast media (ICM) for computerised tomography (CT) increases the risk of acute kidney injury (AKI) and long-term decline in renal function in patients treated in intensive care.METHODS: A retrospective bi-centre cohort study was performed with critically ill subjects undergoing either ICM-enhanced or unenhanced CT. AKI was defined and staged based on the Kidney Disease Improve Global Outcome AKI criteria, using both creatinine and urine output criteria. Follow-up plasma creatinine was recorded three to six months after CT to assess any long-term effects of ICM on renal function.RESULTS: In total, 611 patients were included in the final analysis, median age was 65.0 years (48.0-73.0, quartile 1-quartile 3 (IQR)) and 62.5% were male. Renal replacement therapy was used post-CT in 12.9% and 180-day mortality was 31.2%. Plasma creatinine level on day of CT was 100.0 µmol/L (66.0-166.5, IQR) for non-ICM group and 77.0 µmol/L (59.0-109.0, IQR) for the ICM group. The adjusted odds ratio for developing AKI if the patient received ICM was 1.03 (95% confidence interval 0.64-1.66, p = 0.90). No significant association between ICM and increase in plasma creatinine at long-term follow-up was found, with an adjusted effect size of 2.92 (95% confidence interval - 6.52-12.36, p = 0.543).CONCLUSIONS: The results of this study do not indicate an increased risk of AKI or long-term decline in renal function when ICM is used for enhanced CT in patients treated at intensive care units.CLINICAL RELEVANCE STATEMENT: Patients treated in intensive care units had no increased risk of acute kidney injury or persistent decline in renal function after contrast-enhanced CT. This information underlines the need for a proper risk-reward assessment before denying patients a contrast-enhanced CT.KEY POINTS: • Iodine contrast media is considered a risk factor for the development of acute kidney injury. • Patients receiving iodine contrast media did not have an increased incidence of acute kidney injury or persistent decline in renal function. • A more clearly defined risk of iodine contrast media helps guide clinical decisions whether to perform contrast-enhanced CTs or not.
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- Andersson, Magnus, et al.
(author)
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How cultural values are reflected on the housing market : direct effects and the cultural spillover
- 2019
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In: International Journal of Housing Markets and Analysis. - : Emerald Group Publishing Limited. - 1753-8270 .- 1753-8289. ; 12:3, s. 405-423
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Journal article (peer-reviewed)abstract
- Purpose: The purpose of this paper is to analyse two questions. First, is there, and if so, how large is the price premium paid for a building exhibiting a cultural value? Second, are there any spillover effects of buildings with cultural values on sales prices of neighbouring houses? Design/methodology/approach: Using a unique database of all buildings in the region of Halland, Sweden, combined with transaction data, hedonic models can be estimated, with spatially lagged variables describing proximity to three classes of culturally classified building – A, B and C – corresponding to building of national interest, building of regional interest and building of local interest. In addition, the authors also estimate models with a spatial specification on the error term, in an attempt to control for omitted variables. Findings: The results indicate that cultural classification plays a role in determining the price of a property, with large effects (ranging between 36 and 60% price premiums) for the highest classification. In addition, the authors find evidence of a cultural externality, houses in the vicinity of building with high cultural value sell at a small, but statistically significant premium of 1%. Originality/value: The cultural externality may be overlooked when it comes to valuation of cultural values in society, and therefore, it is likely that warranted protection acts to preserve cultural values in buildings become less than the social optimum. This paper suggests a new measure to cultural values contrasting previous research that rely on cultural preservation. This approach should limit problems with measurement errors that may lead to biased results.
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5. |
- Backman, Fredrik
(author)
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Energy efficiency in Swedish SMEs : Exploring barriers, knowledge creation and the role of municipal energy efficiency programs
- 2018
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Doctoral thesis (other academic/artistic)abstract
- The overall aim of this thesis is to analyze how municipalities support small and medium-sized enterprises (SMEs) in their work to improve their energy efficiency. The purpose of this study is to increase the current understanding of how the methods and tools used by municipalities to assist SMEs in improving their energy efficiency influence the end results in terms of achieved energy efficiency, and how knowledge related to energy efficiency is created within SMEs. This thesis consists of two separate case studies that examine how two municipalities used a network approach to support SMEs in implementing energy efficient measures. The theoretical frameworks of policy networks, barriers, communities of practice (COPs), and energy efficiency networks were used in this thesis. The findings are presented in the appended four articles. An overall conclusion is that networks that provide information in the form of a report with technological solutions as the only output are less likely to reach the agreed-upon goals. To achieve a more successful result, SMEs must be active in the process; they must be allowed to create knowledge and understanding that they perceive as valuable and relevant for themselves. Another important result is that information is not automatically transformed by SMEs into knowledge. In fact, SMEs need a platform from which they can negotiate the received information and use it to create knowledge through practice and social interaction. Finally, it was found that the type of technological solution is not insignificant; the type of energy efficient measure to be implemented and its level of complexity affect how a municipality should support energy efficiency work among SMEs.
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6. |
- Barbu, Andreea, et al.
(author)
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The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets
- 2015
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In: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 97, s. 124-129
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Journal article (peer-reviewed)abstract
- The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo. (C) 2014 The Authors. Published by Elsevier Inc.
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7. |
- Berg, Christoffer, 1986-
(author)
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Public Planning, Neoliberal Hybridity and Local Activism in Sundbyberg : Epochal Reconfiguration of Urban Development in Greater Stockholm
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Which urban policy responses are deployed when a small social democratic municipality in a greater city region aims to be competitive for private investments in housing and the built environment? Which new institutional development arrangements are implemented for this purpose, in the wake of a decades-long hegemonic position of the municipal public housing company? This thesis draws on a qualitative case study design to approach such questions, and investigates recent urban development in Sundbybergs stad in Greater Stockholm to answer them. Theoretically, the thesis draws on a theory of neoliberal localization in combination with Henri Lefebvre’s theory of the social production of space. The thesis is thereby able to explain how the municipality consolidated political power, institutional infrastructures, and administrative capacities with a view to introducing a market-based paradigm of urban development. It argues that this paradigm became characterized by a neoliberal hybridity. It supports this argument by analyzing three major development projects targeting three areas with very different sociospatial characteristics. The thesis thereby demonstrates how market-based developments integrated a number of regulatory features and public planning interventions in accordance with certain objectives, concerns, and conditions. E.g., it reveals how the development of a 1970s Million Homes Programme area, Hallonbergen, relied both on an extended sale of public assets to support private developers’ investments with the objective of comprehensively transforming the area, and on extraordinary measures for ‘social sustainability’. It also reveals how the development of the original municipal town, Central Sundbyberg, was arranged in a municipal development company. This established a business-like format for political control and external expertise, while undermining public planning and clouding democratic accountability. This point is further emphasized by analyzing local inhabitants’ methods for contesting certain development features and land use proposals in this project, enforcing a re-politicization of a largely depoliticized development project. Ultimately, the thesis contributes new knowledge on the variegating forms of neoliberal urbanism through an atypical case of a subordinate city region municipality that historically has been characterized by social democracy, a large public rental housing structure, a public housing company with control of spatial planning, and working-class populations and industries.
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8. |
- Bergman, Hilde-Marlene, et al.
(author)
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Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging
- 2019
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In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 411:13, s. 2809-2816
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Journal article (peer-reviewed)abstract
- Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes.
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9. |
- Berntson, Lillemor, 1957-, et al.
(author)
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Haptoglobin in Juvenile Idiopathic Arthritis
- 2022
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In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 20:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Haptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.METHODS: Plasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).RESULTS: At 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).CONCLUSION: Hp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.
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10. |
- Buckland, Philip I., et al.
(author)
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Integrating human dimensions of Arctic palaeoenvironmental science : SEAD – the strategic environmental archaeology database
- 2011
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In: Journal of Archaeological Science. - : Elsevier. - 0305-4403 .- 1095-9238. ; 38:2, s. 345-351
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Journal article (peer-reviewed)abstract
- Environmental change has a human dimension, and has had so for at least the last 10 000 years. The prehistoric impact of people on the Arctic landscape has occasionally left visible traces, such as house and field structures. More often than not, however, the only evidence available is at the microscopic or geochemical level, such as fossil insect and seed assemblages or changes in the physical and chemical properties of soils and sediments. These records are the subject of SEAD, a multidisciplinary database and software project currently underway at Umeå University, Sweden, which aims to create an online database and set of tools for investigating these traces, as part of an international research infrastructure for palaeoecology and environmental archaeology.
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12. |
- Buckland, Philip I., 1973-, et al.
(author)
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The Strategic Environmental Archaeology Database : a resource for international, multiproxy and transdisciplinary studies of environmental and climatic change
- 2015
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Conference paper (peer-reviewed)abstract
- Climate and environmental change are global challenges which require global data and infrastructure to investigate. These challenges also require a multi-proxy approach, integrating evidence from Quaternary science and archaeology with information from studies on modern ecology and physical processes among other disciplines. The Strategic Environmental Archaeology Database (SEAD http://www.sead.se) is a Swedish based international research e-infrastructure for storing, managing, analysing and disseminating palaeoenvironmental data from an almost unlimited number of analysis methods. The system currently makes available raw data from over 1500 sites (>5300 datasets) and the analysis of Quaternary fossil insects, plant macrofossils, pollen, geochemistry and sediment physical properties, dendrochronology and wood anatomy, ceramic geochemistry and bones, along with numerous dating methods. This capacity will be expanded in the near future to include isotopes, multi-spectral and archaeo-metalurgical data. SEAD also includes expandable climate and environment calibration datasets, a complete bibliography and extensive metadata and services for linking these data to other resources. All data is available as Open Access through http://qsead.sead.se and downloadable software. SEAD is maintained and managed at the Environmental Archaeology Lab and HUMlab at Umea University, Sweden. Development and data ingestion is progressing in cooperation with The Laboratory for Ceramic Research and the National Laboratory for Wood Anatomy and Dendrochronology at Lund University, Sweden, the Archaeological Research Laboratory, Stockholm University, the Geoarchaeological Laboratory, Swedish National Historical Museums Agency and several international partners and research projects. Current plans include expanding its capacity to serve as a data source for any system and integration with the Swedish National Heritage Board's information systems. SEAD is partnered with the Neotoma palaeoecology database (http://www.neotomadb.org) and a new initiative for building cyberinfrastructure for transdisciplinary research and visualization of the long-term human ecodynamics of the North Atlantic funded by the National Science Foundation (NSF).
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13. |
- Bulut, Mehmet Börühan, 1987-
(author)
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Building as active elements of energy systems
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Buildings account for approximately 40% of the energy demand and 33% of the total greenhouse gas emissions in the European Union. Accordingly, there are several efforts that target energy efficiency in buildings both at the European and Swedish levels. The role of buildings in climate change mitigation, however, is not limited to energy savings. Buildings are expected to become key elements of the future smart energy systems by supplying and using energy in a more flexible way. Reducing the energy demand in buildings effectively and shifting the role of buildings in energy systems from ‘passive’ consumers to ‘active’ prosumers, however, require close interaction and cooperation between the energy and buildings sectors.Based on the data collected from interviews and a web survey, this doctoral thesis investigates the relationship between the energy and buildings sectors in Sweden at the inter-company level, presents key stakeholder views on smart energy features in buildings and investigates the opportunities and barriers for their adoption in Sweden and Hong Kong.The results of this thesis suggest a potential for improving the cooperation between the Swedish energy and buildings sectors, which was identified to be influenced by the following factors: district heating monopolies; energy efficiency efforts in the buildings sector; unsuccessful technology-neutrality of the building regulations; self-generation systems in buildings; and energy use patterns. Shifting the focus from self-gains to mutual gains appears crucial to strengthen the inter-sectoral cooperation, as there are several opportunities for achieving mutually beneficial solutions for the two sectors. This would, however, require significant changes in current practices and business models as well as the introduction of new technologies, which would allow for a more flexible energy supply and use. Accordingly, technologies that target flexible energy use in buildings are considered the most important smart energy features in buildings. The current high costs of technologies, such as home automation and smart electrical appliances, however, create the strongest barrier to adoption. Therefore, the introduction of new business and ownership models and the elimination of the institutional and regulatory barriers are crucial to achieve a wide-scale development of smart energy features in buildings. The results from Hong Kong suggest that institutional and regulatory barriers can particularly create strong hinders to the adoption of technologies.It is possible to achieve more sustainable energy systems, where buildings are active elements of networks that supply and use energy in a more flexible and ‘smarter’ way. Cooperation between the energy and buildings sectors can play a key role in the adoption of smart energy features in buildings and pave the way for the smart built environment of the future.
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14. |
- Burden, Håkan, et al.
(author)
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Självkörande landsbygd
- 2021
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Reports (other academic/artistic)abstract
- Hur skulle autonoma fordon kunna användas inom kollektivtrafiken på landsbygden? Genom intervjuer, workshops och en RFI (request for information, ett första steg mot upphandling) har vi undersökt frågan utifrån fyra konkreta områden i Sverige – Lund, Gotland, Eskilstuna och Skellefteå. Med en definition av landsbygd baserad på individens mobilitet har vi sett att Sveriges landsbygd rymmer mindre orter på väg att avfolkas där äldre, barn och de utan körkort hade kunnat få bättre tillgång till samhällelig service med autonoma fordon. Vi har också sett att flera av landets nya arbetsplatser kommer befinna sig på landsbygden och därmed skapa ett mobilitetsbehov från staden till landet. För att kunna realisera de identifierade möjligheterna finns ett behov av att framföra fordonen i högre hastigheter samt att de ska kunna hantera mer komplexa trafiksituationer än vad dagens piloter i städerna visat. På landsbygden finns alltså ett utrymme för nya fordon att visa upp sig. Samtidigt ser vi hur man inte ska förvänta sig att investeringarna i autonoma fordon kommer betala sig på en linje, snarare behöver man lyfta blicken och se systemeffekten när stomlinjetrafiken blir mer attraktiv då bussarna går raka vägen istället för via mindre samhällen. Vi har inte sett några belägg på att den digitala infrastrukturen behöver utvecklas för att möjliggöra försök med autonoma fordon på någon av de undersökta rutterna. Dagens 4G-täckning är fullgod och fordonen borde ha tillgång till tillräckligt bra positioneringsdata för att bedriva verksamheten. Däremot ställs flera frågor om hur ersättningstrafiken organiseras när fordonen inte klarar av vädret, vem som står för säkrare hållplatser och hur chaufförens övriga ansvar realiseras när fordonet är förarlöst.
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15. |
- Burmakin, Mikhail, et al.
(author)
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Pharmacological HIF-PHD inhibition reduces renovascular resistance and increases glomerular filtration by stimulating nitric oxide generation
- 2021
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In: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 233:1
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Journal article (peer-reviewed)abstract
- AIM: Hypoxia-inducible factors (HIFs) are O2 -sensitive transcription factors that regulate multiple biological processes which are essential for cellular adaptation to hypoxia. Small molecule inhibitors of HIF-prolyl hydroxylase domain (PHD) dioxygenases (HIF-PHIs) activate HIF-dependent transcriptional programs and have broad clinical potential. HIF-PHIs are currently in global late-stage clinical development for the treatment of anaemia associated with chronic kidney disease. Although the effects of hypoxia on renal haemodynamics and function have been studied in animal models and in humans living at high altitude, the effects of pharmacological HIF activation on renal haemodynamics, O2 metabolism and metabolic efficiency are not well understood.METHODS: Using a cross-sectional study design, we investigated renal haemodynamics, O2 metabolism, gene expression and NO production in healthy rats treated with different doses of HIF-PHIs roxadustat or molidustat compared to vehicle control.RESULTS: Systemic administration of roxadustat or molidustat resulted in a dose-dependent reduction in renovascular resistance (RVR). This was associated with increased glomerular filtration rate (GFR), urine flow and tubular sodium transport rate (TNa ). Although both total O2 delivery and TNa were increased, more O2 was extracted per transported sodium in rats treated with high-doses of HIF-PHIs, suggesting a reduction in metabolic efficiency. Changes in RVR and GFR were associated with increased nitric oxide (NO) generation and substantially suppressed by pharmacological inhibition of NO synthesis.CONCLUSIONS: Our data provide mechanistic insights into dose-dependent effects of short-term pharmacological HIF activation on renal haemodynamics, glomerular filtration and O2 metabolism and identify NO as a major mediator of these effects.
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16. |
- Carlsson, Per-Ola, et al.
(author)
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Chronically decreased oxygen tension in rat pancreatic islets transplantedunder the kidney capsule
- 2000
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 69:5, s. 761-766
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Journal article (peer-reviewed)abstract
- BACKGROUND: A factor of potential importance in the failure of islet grafts is poor or inadequate engraftment of the islets in the implantation organ. This study measured the oxygen tension and blood perfusion in 1-, 2-, and 9-month-old islet grafts. METHODS: The partial pressure of oxygen was measured in pancreatic islets transplanted beneath the renal capsule of diabetic and nondiabetic recipient rats with a modified Clark electrode (outer tip diameter 2-6 microm). The size of the graft (250 islets) was by purpose not large enough to cure the diabetic recipients. The oxygen tension in islets within the pancreas was also recorded. Blood perfusion was measured with the laser-Doppler technique. RESULTS: Within native pancreatic islets, the partial pressure of oxygen was approximately 40 mm Hg (n=8). In islets transplanted to nondiabetic animals, the oxygen tension was approximately 6-7 mm Hg 1, 2, and 9 months posttransplantation. No differences could be seen between the different time points after transplantation. In the diabetic recipients, an even more pronounced decrease in graft tissue oxygen tension was recorded. The mean oxygen tension in the superficial renal cortex surrounding the implanted islets was similar in all groups (approximately 15 mm Hg). Intravenous administration of glucose (0.1 gxkg(-1)x min(-1)) did not affect the oxygen tension in any of the investigated tissues. The islet graft blood flow was similar in all groups, measuring approximately 50% of the blood flow in the kidney cortex. CONCLUSION: The oxygen tension in islets implanted beneath the kidney capsule is markedly lower than in native islets up to 9 months after transplantation. Moreover, persistent hyperglycemia in the recipient causes an even further decrease in graft oxygen tension, despite similar blood perfusion. To what extent this may contribute to islet graft failure remains to be determined.
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24. |
- Carlström, Eric, 1957, et al.
(author)
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Medical Emergencies During a Half Marathon Race - The Influence of Weather
- 2019
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In: International Journal of Sports Medicine. - Stuttgart : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 40:5, s. 312-316
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Journal article (peer-reviewed)abstract
- The aim was to analyze the influence of weather conditions on medical emergencies in a half-marathon, specifically by evaluating its relation to the number of non-finishers, ambulance-required assistances, and collapses in need of ambulance as well as looking at the location of such emergencies on the race course. Seven years of data from the world's largest half marathon were used. Meteorological data were obtained from a nearby weather station, and the Physiological Equivalent Temperature (PET) index was used as a measure of general weather conditions. Of the 315,919 race starters, 104 runners out of the 140 ambulance-required assistances needed ambulance services due to collapses. Maximum air temperature and PET significantly co-variated with ambulance-required assistances, collapses, and non-finishers (R (2) =0.65-0.92; p=0.001-0.03). When air temperatures vary between 15-29 degrees C, an increase of 1 degrees C results in an increase of 2.5 (0.008/1000) ambulance-required assistances, 2.5 (0.008/1000) collapses (needing ambulance services), and 107 (0.34/1000) non-finishers. The results also indicate that when the daily maximum PET varies between 18-35 degrees C, an increase of 1 degrees C PET results in an increase of 1.8 collapses (0.006/1000) needing ambulance services and 66 non-finishers (0.21/1000).
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25. |
- Carlström, Mattias, et al.
(author)
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Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals
- 2008
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In: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 294:2, s. 362-370
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Journal article (peer-reviewed)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.
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