| 1. |
- Kashioulis, Pavlos, 1980, et al.
(författare)
-
Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction
- 2018
-
Ingår i: Kidney & Blood Pressure Research. - : S. Karger AG. - 1420-4096 .- 1423-0143. ; 43:4, s. 1053-1064
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Rats with adenine-induced chronic renal failure (ACRF) develop severe renal insufficiency and metabolic abnormalities that closely resemble those in patients with uremia. The aim of the present study was to determine left ventricular (LV) morphology and function in rats with ACRF. Methods: Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls, C). After 9-13 weeks animals were anesthetized with isoflurane and cardiac function was assessed both by echocardiography and by LV catheterization. Results: Rats with ACRF showed increases in serum creatinine (323 +/- 107 vs. 33 +/- 5 pM, P<0.05), mean arterial pressure (115 +/- 6 vs. 106 +/- 7 mmHg, P<0.05) and LV weight (3.4 +/- 0.3 vs. 2.5 +/- 0.2 mg/kg, P<0.05) vs. controls. Rats with ACRF had reduced early diastolic tissue Doppler velocities in the LV, enlarged left atrial diameter (4.8 +/- 0.8 vs. 3.5 +/- 0.4 mm, P<0.05) and elevated LV end-diastolic pressure (15 +/- 5 vs. 8 +/- 1 mmHg, P <0.01). Cardiac output was increased in ACRF rats (211 +/- 66 vs. 149 +/- 24 ml/min, P <0.05) and systolic function preserved. In the LV of ACRF rats there were statistically significant (P<0.05) increases in cardiomyocyte diameter, proliferation and apoptosis, while there was no difference between groups in fibrosis. Conclusion: Rats with ACRF develop LV hypertrophy and diastolic dysfunction while systolic performance was preserved. There was an increased hypertrophy and apoptosis of cardiomyocytes in the LV of ACRF rats. The cardiac abnormalities in ACRF rats resemble those in patients with CKD in which heart failure with preserved ejection fraction is common. Hence, this experimental model is well suited for studying pathophysiological mechanisms in chronic renocardiac syndromes. (C) 2018 The Author(s) Published by S. Karger AG, Basel
|
|
| 2. |
- Kashioulis, Pavlos, 1980, et al.
(författare)
-
Patients with moderate chronic kidney disease without heart disease have reduced coronary flow velocity reserve
- 2020
-
Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 2797-2805
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The overall aim was to identify sub-clinical cardiac abnormalities by echocardiography in patients with chronic kidney disease (CKD) stages 3 and 4 and to investigate underlying mechanisms. Methods and results Ninety-one patients with CKD stages 3 and 4, without a diagnosis of heart disease, and 41 healthy matched controls were included in this cross-sectional study. Cardiac morphology and function were analysed with Doppler echocardiography and coronary flow velocity reserve (CFVR) in response to adenosine was measured in the left anterior descendent artery to detect coronary microvascular dysfunction (CMD). All study subjects had a left ventricular (LV) ejection fraction > 50%. Patients with CKD showed statistically significant increases in left atrial volume index and transmitral and pulmonary vein flow velocities during atrial contraction and prolonged LV isovolumetric relaxation time. Patients with CKD had significantly reduced CFVR vs. controls (2.74 +/- 0.86 vs. 3.40 +/- 0.89, P < 0.001), and 43% of patients were classified as having CMD compared with 9% of controls (P = 0.001). Conclusions Patients with CKD stages 3 and 4, without a diagnosis of heart disease, showed early abnormalities in LV diastolic function that did not fulfil the criteria for LV dysfunction according to current guidelines. A large proportion of CKD patients had CMD, suggesting that microvascular abnormalities may have a pathogenic role in the development of heart failure in this patient group.
|
|
| 3. |
- Alhadad, Alaa, et al.
(författare)
-
Renal angioplasty causes a rapid transient increase in inflammatory biomarkers, but reduced levels of interleukin-6 and endothelin-1 1 month after intervention.
- 2007
-
Ingår i: Journal of hypertension. - 0263-6352 .- 1473-5598. ; 25:9, s. 1907-14
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine prospectively whether inflammatory biomarkers and endothelin (ET)-1 are increased in patients with renal artery stenosis (RAS), and to investigate how treatment with percutaneous transluminal renal angioplasty (PTRA) affects these variables during the first month after intervention. METHODS: One hundred patients with suspected RAS undergoing renal angiography were included. PTRA was performed if the trans-stenotic mean arterial pressure gradient was>or=10 mmHg. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), neopterin, CD40 ligand (CD40L) and endothelin-1 (ET-1) were measured before, and 1 day and 1 month after PTRA (n=61) or diagnostic angiography only (n=39). RESULTS: At baseline there were no significant differences in inflammatory biomarkers or ET-1 levels between patients subsequently undergoing PTRA or angiography only. After angiography, IL-6 and hs-CRP had increased in both groups compared to baseline (P<0.001). At this time point hs-CRP (10.90+/-1.48 versus 6.37+/-1.61 mg/l; P<0.05) and IL-6 (13.70+/-0.94 versus 13.00+/-0.17 pg/ml; P<0.01) were higher in the PTRA group than in patients subjected to angiography only. One month after PTRA, systolic blood pressure and levels of IL-6 and ET-1 were lower than before intervention (P<0.05), whereas CD40L had increased compared to baseline (P<0.01). CONCLUSION: In patients with RAS, PTRA triggers rapid transient increases in hs-CRP and IL-6; however, 1 month after PTRA, both IL-6 and ET-1 had decreased compared to before intervention, indicating beneficial effects of PTRA on inflammation and the endothelin system.
|
|
| 4. |
- Elíasdóttir, Sigridur, et al.
(författare)
-
Serum levels of galactose-deficient IgA are elevated in patients with IgA nephropathy but do not correlate to disease activity or progression
- 2023
-
Ingår i: Bmc Nephrology. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionIgA nephropathy (IgAN) is the most common glomerulonephritis globally. Because of the heterogeneity of the disease prognostic biomarkers are highly needed.AimTo investigate associations between galactose-deficient IgA1 (Gd-IgA1) concentrations in plasma and urine and disease activity and progression in patients with IgAN.MethodsSerum and urine samples were collected at the time of kidney biopsy (baseline) in patients with IgAN (n = 40) and analysed for Gd-IgA1. Patients with chronic kidney disease (CKD) without IgAN (n = 21) and healthy controls (n = 19) were examined as controls. In 19 patients with IgAN, analyses of Gd-IgA1 were repeated after a median follow up time of approximately 10 years.ResultsSerum Gd-IgA1 and Gd-IgA1:IgA were significantly elevated at the time of kidney biopsy in patients with IgAN compared to patients with non-IgAN CKD and healthy controls (p < 0.001). Urinary Gd-IgA1:creatinine was significantly elevated in patients with IgAN compared to patients with non-IgAN CKD. Neither serum Gd-IgA1, nor serum Gd-IgA1:IgA, correlated significantly to estimated GFR, urine albumin:creatinine (UACR), or blood pressure, at baseline. Serum Gd-IgA1 and Gd-IgA1:IgA at time of biopsy did not correlate significantly to annual changes in eGFR or UACR during follow up. In patients with IgAN, serum Gd-IgA1 decreased significantly over time during approximately 10 years of follow up (Delta-20 +/- 85%, p = 0.027). Urinary Gd-IgA1:creatinine showed a strong positive correlation to UACR in patients with IgAN and likely reflected unspecific glomerular barrier injury.ConclusionAlthough serum Gd-IgA1 and the Gd-IgA1:IgA ratio were significantly elevated in patients with IgAN at the time of kidney biopsy they were not related to disease activity or progression in this patient cohort.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Guron, Gregor, 1967, et al.
(författare)
-
Acute effects of the superoxide dismutase mimetic tempol on split kidney function in two-kidney one-clip hypertensive rats.
- 2006
-
Ingår i: Journal of hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 24:2, s. 387-94
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the acute effects of the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) on split kidney function, and renal haemodynamics, in two-kidney, one-clip (2K1C) hypertensive rats. METHODS: Three weeks after clipping, or the sham procedure, the effects of intravenous tempol (200 micromol/kg per h) were evaluated on thiobutabarbital anaesthetized Sprague-Dawley rats. RESULTS: Mean arterial pressure (MAP; 152 +/- 3 versus 122 +/- 3 mmHg, P < 0.001), plasma renin activity (28.7 +/- 3.0 versus 9.5 +/- 0.6 ng/ml per h, P < 0.001) and urinary 8-iso-prostaglandin F2alpha excretion (124 +/- 4 versus 92 +/- 10 pmol/24 h, P = 0.003) were significantly elevated in 2K1C rats compared with sham. Tempol reduced MAP by 15 +/- 1% compared with baseline (P < 0.001) in 2K1C rats. In clipped kidneys, tempol increased the glomerular filtration rate (GFR; +50 +/- 15% from baseline) and the effective renal plasma flow (ERPF; +37 +/- 13%, from baseline), and reduced renal vascular resistance (RVR; -32 +/- 6% from baseline) compared with saline-treated controls (P < 0.05). In non-clipped kidneys, tempol reduced RVR (-24 +/- 5% from baseline) compared with saline-treated controls (P = 0.001). In sham-operated rats, tempol produced a modest reduction in MAP (-8 +/- 2% from baseline, P = 0.003), but did not significantly affect renal haemodynamics or function. CONCLUSION: Tempol reduced MAP and RVR in both clipped and non-clipped kidneys of 2K1C hypertensive rats. In addition, tempol increased ERPF and GFR in the clipped kidney. These findings suggest important roles for superoxide in the regulation of renal haemodynamics during the early maintenance phase of renovascular hypertension.
|
|
| 8. |
- Guron, Gregor, 1967, et al.
(författare)
-
Acute renal failure after a holiday in the tropics.
- 2006
-
Ingår i: Clinical nephrology. - 0301-0430. ; 66:6, s. 468-71
-
Tidskriftsartikel (refereegranskat)abstract
- A 20-year-old, previously healthy woman, presented with high fever, headache and myalgia 3 days after her return from a holiday in Southeast Asia. Laboratory data on admission demonstrated a pronounced increase in plasma creatinine, marked thrombocytopenia and moderately elevated liver aminotransferases. After having ruled out malaria, dengue fever was primarily suspected and supportive intravenous fluid therapy was initiated. Still, 1 day after admission, platelet counts dropped even further and she became anuric although she did not appear hypovolemic. On day 2 after admission, urine production commenced spontaneously and the patient slowly recovered. All laboratory test results had returned to normal approximately 2 months later. Serological analysis for dengue fever was negative. It turned out that the patient had been trekking in the jungle while in Thailand and we, therefore, analyzed serology for Leptospira spirochetes which was clearly positive. The patient was diagnosed with leptospirosis which is a serious condition associated with a high mortality when complicated by acute renal failure. Differential diagnoses in patients with acute renal failure and tropical infections are reviewed. The importance of early recognition of leptospirosis, and prompt treatment with antibiotics in suspected cases, is emphasized.
|
|
| 9. |
- Guron, Gregor, 1967, et al.
(författare)
-
Cardiac insulin-like growth factor I and growth hormone receptor expression in renal hypertension
- 1996
-
Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 27:3/Pt 2, s. 636-42
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the role of insulin-like growth factor I in the development of cardiac hypertrophy in two-kidney, one clip hypertension by relating growth hormone receptor and insulin-like growth factor I receptor mRNA levels to insulin-like growth factor I gene transcription using a solution hybridization/RNase protection assay. Two-kidney, one clip hypertension was induced in male Wistar rats, and experiments were performed 2, 4, 7, and 12 days after surgery. Systolic blood pressure was elevated 2, 7, and 12 days after clipping (P < .001). Left ventricular weights were increased 2, 4, 7, and 12 days after surgery (P < .01). Associated with the rise in blood pressure, left ventricular insulin-like growth factor I mRNA was increased 2, 7, and 12 days after surgery (P < .01). Furthermore, growth hormone receptor and insulin-like growth factor I receptor gene expression increased specifically in the left ventricle of renal hypertensive rats (P < .05 and P < .001, respectively). Left ventricular growth hormone receptor mRNA peaked 7 days after induction of renal artery stenosis. These results show that insulin-like growth factor I, growth hormone receptor, and insulin-like growth factor I receptor mRNA increase in the pressure-overloaded left ventricle of two-kidney, one clip rats, suggesting a role for insulin-like growth factor I and the growth hormone/insulin-like growth factor I axis in the development of cardiac hypertrophy.
|
|
| 10. |
|
|
| 11. |
- Jansson, Hanna, 1975, et al.
(författare)
-
Impact of Abdominal Aortic Calcification on Central Haemodynamics and Decline of Glomerular Filtration Rate in Patients with Chronic Kidney Disease Stages 3 and 4
- 2019
-
Ingår i: Kidney and Blood Pressure Research. - : KARGER. - 1420-4096 .- 1423-0143. ; 44:5, s. 950-960
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Calcifications of large arteries are frequent in chronic kidney disease (CKD) and may contribute to the high cardiovascular risk in this population. The aim of this study was to examine whether abdominal aortic calcification volume (AACV) was a predictor of the rate of decline in glomerular filtration rate (GFR) in a cohort of patients with CKD stages 3 and 4. Methods: Eighty-four patients with CKD stages 3 and 4 were enrolled in this prospective observational study. At study entry, and annually, GFR was measured by plasma Cr-51-EDTA clearance. At baseline, haemodynamics was assessed and AACV was determined by computer tomography. Results: The mean follow-up time was 3.4 years and mean decline in GFR was -2.69 mL/min/1.73 m(2) per year. At baseline, abdominal aortic calcification (AAC) was detected in 66 patients (79%). A binary logistic regression analysis revealed that age was the only statistically significant independent predictor of AAC. In patients with AAC, male gender (B = 0.413, p = 0.030), aortic diastolic blood pressure (B = -0.025, p = 0.001) and ankle-brachial index (B = -1.666, p = 0.002) were independently associated with AACV using a multiple linear regression analysis. Neither the presence nor the extent of AAC was significantly associated with the rate of change in GFR during follow-up. Conclusion: In this cohort of patients with CKD stages 3 and 4, only age was an independent predictor of the presence of AAC. AACV was not associated with the rate of decline in GFR. (c) 2019 The Author(s)
|
|
| 12. |
- Kashioulis, Pavlos, 1980, et al.
(författare)
-
High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels
- 2016
-
Ingår i: Cardiorenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 6:4, s. 317-327
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). Methods: Male Sprague-Dawley rats either received chow containing adenine or were pair-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. Results: Rats with ACRF showed statistically significant increases (p < 0.001) in arterial pressure (AP), LV weight and fibrosis, and serum cTnT levels compared to controls. Two weeks of high-NaCl intake augmented the increases in AP, LV weight and fibrosis, and serum cTnT concentrations only in ACRF rats (p < 0.05 for group x NaCl intake interaction). Compared to group C-NNa, cTnT levels were elevated approximately 6-fold in group ACRF-NNa and 24-fold in group ACRF-HNa. Focal LV injury with cardiomyocyte necrosis, scarring, and fibrinoid necrosis of small arteries were only detected in group ACRF-HNa. There was a strong correlation between the degree of LV fibrosis and serum cTnT levels in ACRF rats (r = 0.81, p < 0.01). Conclusion: Two weeks of high-NaCl diet in rats with ACRF produces LV injury and aggravates increases in serum cTnT levels, presumably by causing hypertension-induced small artery lesions leading to myocardial ischemia. This model may be suitable for studying pathophysiological mechanisms in chronic renicardiac syndromes. (C) 2016 S. Karger AG, Basel
|
|
| 13. |
- Lasaitiene, Daina, 1970, et al.
(författare)
-
Perturbed medullary tubulogenesis in neonatal rat exposed to renin-angiotensin system inhibition.
- 2003
-
Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - 0931-0509. ; 18:12, s. 2534-41
-
Tidskriftsartikel (refereegranskat)abstract
- Pharmacological interruption of the angiotensin II type-1 receptor (AT(1)) signalling during nephrogenesis in rats induces irreversible abnormalities in kidney morphology, comprising papillary atrophy and tubulointerstitial damage, which are characterized by tubular dilatation/atrophy and interstitial inflammation/fibrosis. This study determined the time course for development of tubular structural and inflammatory changes and possible cytokine production in the renal medulla of newborn rats exposed to angiotensin-converting enzyme (ACE) inhibition. Additionally, medullary expression of E-cadherin, a marker for tubular formation, was investigated in ACE-inhibited rats.
|
|
| 14. |
- Nguy, Lisa, 1985, et al.
(författare)
-
Adenine-induced chronic renal failure in rats decreases aortic relaxation rate and alters expression of proteins involved in vascular smooth muscle calcium handling
- 2016
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 218:4, s. 250-264
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Rats with adenine-induced chronic renal failure (A-CRF) develop a reduced rate of relaxation of the thoracic aorta. The aim of this study was to elucidate the mechanisms underlying this abnormality. Methods: Male Sprague Dawley rats received either chow containing adenine or were pair-fed with normal chow (controls). After 8–14 weeks, arterial function was analysed ex vivo using wire myography and the expression of proteins involved in vascular smooth muscle excitation–contraction coupling in the thoracic aorta was analysed. Results: The rate of relaxation following washout of KCl was reduced in A-CRF rats vs. controls in the thoracic aorta (P
|
|
| 15. |
- Nguy, Lisa, 1985, et al.
(författare)
-
Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness
- 2013
-
Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 304:9
-
Tidskriftsartikel (refereegranskat)abstract
- Rats with adenine-induced chronic renal failure (A-CRF) develop metabolic and cardiovascular abnormalities resembling those in patients with chronic kidney disease. The aim of this study was to investigate the mechanisms of hypertension in this model and to assess aortic stiffness in vivo. Male Sprague-Dawley rats were equipped with radiotelemetry probes for arterial pressure recordings and received either chow containing adenine or normal control diet. At 7 to 11 wk after study start, blood pressure responses to high NaCl (4%) diet and different pharmacological interventions were analyzed. Aortic pulse wave velocity was measured under isoflurane anesthesia. Baseline 24-h mean arterial pressure (MAP) was 101 +/- 10 and 119 +/- 9 mmHg in controls and A-CRF animals, respectively (P < 0.01). After 5 days of a high-NaCl diet, MAP had increased by 24 +/- 6 mmHg in A-CRF animals vs. 2 +/- 1 mmHg in controls (P < 0.001). Candesartan (10 mg/kg by gavage) produced a more pronounced reduction of MAP in controls vs. A-CRF animals (-12 +/- 3 vs. -5 +/- 5 mmHg, P < 0.05). Aortic pulse wave velocity was elevated in A-CRF rats (5.10 +/- 0.51 vs. 4.58 +/- 0.17 m/s, P < 0.05). Plasma levels of creatinine were markedly elevated in A-CRF animals (259 +/- 46 vs. 31 +/- 2 muM, P < 0.001), whereas plasma renin activity was suppressed (0.6 +/- 0.5 vs. 12.3 +/- 7.3 mug.l(-1).h(-1), P < 0.001). In conclusion, hypertension in A-CRF animals is characterized by low plasma renin activity and is aggravated by high-NaCl diet, suggesting a pathogenic role for sodium retention and hypervolemia probably secondary to renal insufficiency. Additionally, aortic stiffness was elevated in A-CRF animals as indicated by increased aortic pulse wave velocity
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Nguy, Lisa, 1985, et al.
(författare)
-
Vascular function in rats with adenine-induced chronic renal failure.
- 2012
-
Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 302:12
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to characterize the function of resistance arteries, and the aorta, in rats with adenine-induced chronic renal failure (A-CRF). Sprague-Dawley rats were randomized to chow with or without adenine supplementation. After 6-10 wk, mesenteric arteries and thoracic aortas were analyzed ex vivo by wire myography. Plasma creatinine concentrations were elevated twofold at 2 wk, and eight-fold at the time of death in A-CRF animals. Ambulatory systolic and diastolic blood pressures measured by radiotelemetry were significantly elevated in A-CRF animals from week 3 and onward. At death, A-CRF animals had anemia, hyperphosphatemia, hyperparathyroidism, and elevated plasma levels of asymmetric dimethylarginine and oxidative stress markers. There were no significant differences between groups in the sensitivity, or maximal response, to ACh, sodium nitroprusside (SNP), norepinephrine, or phenylephrine in either mesenteric arteries or aortas. However, in A-CRF animals, the rate of aortic relaxation was significantly reduced following washout of KCl (both in intact and endothelium-denuded aorta) and in response to ACh and SNP. Also the rate of contraction in response to KCl was significantly reduced in A-CRF animals both in mesenteric arteries and aortas. The media of A-CRF aortas was thickened and showed focal areas of fragmented elastic lamellae and disorganized smooth muscle cells. No vascular calcifications could be detected. These results indicate that severe renal failure for a duration of less than 10 wk in this model primarily affects the aorta and mainly slows the rate of relaxation.
|
|
| 19. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Angiotensin II Type 1 Receptor Antagonism Attenuates Abnormalities in Dynamic Renal Blood Flow Autoregulation in Rats with Endotoxin-Induced Acute Kidney Injury.
- 2010
-
Ingår i: Kidney & blood pressure research. - : S. Karger AG. - 1423-0143 .- 1420-4096. ; 33:3, s. 200-208
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to examine the role of angiotensin II type 1 receptors in dynamic autoregulation of renal blood flow (RBF) in endotoxemia. Methods: Experiments were performed on anesthetized rats 16 h after intraperitoneal lipopolysaccharide (LPS) or vehicle administration. After baseline measurements, groups Sham-Saline, LPS-Saline and LPS-Candesartan received isotonic saline or candesartan (10 mug kg(-1) i.v.). Data were collected during eight consecutive 20-min clearance periods (C1-8). Transfer function (TF) analysis in the frequency domain was used to examine dynamic autoregulation of RBF. Results: Endotoxemic rats showed an approximate 50% reduction in glomerular filtration rate (GFR) and RBF (p < 0.05 vs. Sham-Saline). Candesartan significantly increased RBF (+40 +/- 6% vs. baseline; p < 0.05) but did not significantly influence GFR. Endotoxemic animals showed a normal myogenic response but had elevated TF gain values in the frequency range of the tubuloglomerular feedback mechanism (TGF; 0.01-0.03 Hz) reflecting impaired autoregulation (periods C3-4, 2.2 +/- 1.6 vs. -2.6 +/- 0.6 dB, p < 0.05, and C7-8, -0.4 +/- 1.3 vs. -4.0 +/- 0.8 dB, p < 0.05; in groups LPS-Saline and Sham-Saline, respectively). Candesartan normalized TF gain in this frequency range (periods C7-8, -6.1 +/- 2.3 dB in group LPS-Candesartan, p < 0.05 vs. LPS-Saline). Conclusion: Candesartan ameliorates the adverse effect of endotoxin on the TGF component of dynamic autoregulation of RBF.
|
|
| 20. |
|
|
| 21. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Effects of N-acetyl-L-cysteine on renal haemodynamics and function in early ischaemia-reperfusion injury in rats.
- 2006
-
Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 0305-1870 .- 1440-1681. ; 33:1-2, s. 53-7
-
Tidskriftsartikel (refereegranskat)abstract
- 1. Renal ischaemia-reperfusion (IR) severely compromises kidney function and has been shown to cause persistent abnormalities in intrarenal blood flow. The aim of the present study was to examine whether N-acetyl-L-cysteine (NAC), a thiol-containing anti-oxidant, improves renal haemodynamics and function during early reperfusion in rats subjected to renal IR. 2. Male Sprague-Dawley rats were divided into groups receiving either isotonic saline (IR-Saline; n = 8) or NAC (IR-NAC; n = 8) prior to (200 mg/kg, i.p., 24 and 12 h before acute experimentation) and during acute renal clearance experiments (bolus 150 mg/kg followed by a continuous infusion of 43 mg/kg per h, i.v.). During acute experimentation, thiobutabarbital-anaesthetized rats were subjected to a right-sided nephrectomy, followed by left kidney IR (40 min renal artery occlusion). Left kidney function and blood flow and intrarenal cortical and outer medullary perfusion measured by laser-Doppler flowmetry was analysed at baseline, during ischaemia and for 80 min of reperfusion. 3. Renal IR produced an approximate 85% reduction in glomerular filtration rate (GFR) and a pronounced increase in fractional urinary sodium excretion, throughout reperfusion, with no statistically significant differences between groups. 4. During reperfusion, total renal blood flow and cortical and outer medullary perfusion rapidly returned to levels not significantly different from baseline in both groups. The relative increase in renal vascular resistance in response to IR was more pronounced in NAC-treated rats compared with saline-treated animals (P < 0.05). 5. In conclusion, treatment with NAC did not improve kidney function during the first 80 min after renal IR. In addition, the marked reduction in GFR following reperfusion was not associated with any detectable abnormalities in intrarenal perfusion.
|
|
| 22. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Effects of thrombin inhibition with melagatran on renal hemodynamics and function and liver integrity during early endotoxemia.
- 2007
-
Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 292:3
-
Tidskriftsartikel (refereegranskat)abstract
- Sepsis is associated with an activation of the coagulation system and multiorgan failure. The aim of the study was to examine the effects of selective thrombin inhibition with melagatran on renal hemodynamics and function, and liver integrity, during early endotoxemia. Endotoxemia was induced in thiobutabarbital-anesthetized rats by an intravenous bolus dose of lipopolysaccharide (LPS; 6 mg/kg). Sham-Saline, LPS-Saline, and LPS-Melagatran study groups received isotonic saline or melagatran immediately before (0.75 micromol/kg iv) and continuously during (0.75 micromol.kg(-1).h(-1) iv) 4.5 h of endotoxemia. Kidney function, renal blood flow (RBF), and intrarenal cortical and outer medullary perfusion (OMLDF) measured by laser-Doppler flowmetry were analyzed throughout. Markers of liver injury and tumor necrosis factor (TNF)-alpha were measured in plasma after 4.5 h of endotoxemia. In addition, liver histology and gene expression were examined. Melagatran treatment prevented the decline in OMLDF observed in the LPS-Saline group (P < 0.05, LPS-Melagatran vs. LPS-Saline). However, melagatran did not ameliorate reductions in mean arterial pressure, RBF, renal cortical perfusion, and glomerular filtration rate or attenuate tubular dysfunctions during endotoxemia. Melagatran reduced the elevated plasma concentrations of aspartate aminotransferase (-34 +/- 11%, P < 0.05), alanine aminotransferase (-21 +/- 7%, P < 0.05), bilirubin (-44 +/- 9%, P < 0.05), and TNF-alpha (-32 +/- 14%, P < 0.05) in endotoxemia. Melagatran did not diminish histological abnormalities in the liver or the elevated hepatic gene expression of TNF-alpha, intercellular adhesion molecule-1, and inducible nitric oxide synthase in endotoxemic rats. In summary, thrombin inhibition with melagatran preserved renal OMLDF, attenuated liver dysfunction, and reduced plasma TNF-alpha levels during early endotoxemia.
|
|
| 23. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Endothelin b receptors preserve renal blood flow in a normotensive model of endotoxin-induced acute kidney dysfunction
- 2008
-
Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322. ; 29:3, s. 402-409
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the role of endothelin 1 receptor subtypes in the early renal response to lipopolysaccharide (LPS) during normotensive endotoxemia with acute kidney dysfunction. Endotoxemia was induced in thiobutabarbital-anesthetized rats (n = 9 per group) by infusion of LPS (dosage, 1 mg/kg per hour i.v.). The study groups (1) sham-saline, (2) LPS-saline, (3) LPS-BQ123, (4) LPS-BQ788 and (5) LPS-BQ123 + BQ788 received isotonic saline, the ETA receptor antagonist BQ-123 (dosage, 30 nmol/kg per minute i.v.), and/or the ETB receptor antagonist BQ-788 (dosage, 30 nmol/kg per minute i.v.) before and during 2 h of LPS infusion. Renal clearance measurements, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (Clark-type microelectrodes) were analyzed throughout. Before LPS administration, there were no significant differences between groups in glomerular filtration rate (GFR), RBF, or in cortical (CLDF) and outer medullary perfusion. However, mean arterial pressure (MAP) was elevated in LPS-BQ788 group compared with LPS-BQ123 + BQ788 group (P < 0.05). In saline-treated rats, endotoxin induced an approximate 35% reduction in GFR (P < 0.05), without significant effects on MAP, RBF, or on CLDF and cortical PO2. In addition, LPS increased outer medullary perfusion and PO2 (P < 0.05). The fractional urinary excretion rates of sodium, potassium, and water were not significantly different in LPS-saline group compared with sham-saline group. Neither selective nor combined ETA and ETB receptor blockade improved GFR. In BQ-788-infused rats, endotoxin produced marked reductions in RBF (-18% +/- 4% [P < 0.05]) and CLDF (-18% +/- 2% [P < 0.05]). Similarly, endotoxin decreased RBF (-14% +/- 3% [P < 0.05]) and CLDF (-10% +/- 2% [P < 0.05]) in LPS-BQ123 + BQ788 group. Endotoxin reduced MAP (-22% +/- 4% [P < 0.05]) in BQ-123-treated rats but did not significantly influence MAP in other groups. We conclude that in early normotensive endotoxemia, ETB receptors exert a renal vasodilator influence and contribute to maintain normal RBF.
|
|
| 24. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Low-dose candesartan improves renal blood flow and kidney oxygen tension in rats with endotoxin-induced acute kidney dysfunction.
- 2008
-
Ingår i: Shock (Augusta, Ga.). - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322. ; 30:2, s. 166-72
-
Tidskriftsartikel (refereegranskat)abstract
- Sepsis is associated with an activation of the renin-angiotensin system and causes acute kidney injury. The aim was to examine the effects of a low, nondepressor dose of the selective angiotensin II type 1 receptor antagonist candesartan on renal hemodynamics and function in endotoxemic rats. Endotoxemia was induced in Sprague-Dawley rats by a dose of LPS (Escherichia coli O127:B8; 7.5 mg kg(-1), i.p.). At 16 h after endotoxin administration, renal clearance experiments were performed in thiobutabarbital anesthetized rats. Study groups (1) sham-saline, (2) LPS-saline, and (3) LPS-candesartan received isotonic saline or candesartan (10 microg kg(-1), i.v.) after baseline measurements. Kidney function, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (P(O2); Clark-type microelectrodes) were analyzed during 2 h after drug administration. At baseline, endotoxemic rats showed an approximately 50% reduction in glomerular filtration rate and RBF (P < 0.05), a decline in cortical and outer medullary perfusion, and Po2 (P < 0.05), but no significant alterations in MAP compared with saline-injected controls. Candesartan treatment significantly improved RBF (+40% +/- 6% vs. baseline), cortical perfusion (+18% +/- 3% vs. baseline), and cortical (+19% +/- 7% vs. baseline) and outer medullary (+22% +/- 10% vs. baseline) P(O2) in endotoxemic rats (P < 0.05 vs. LPS-saline). Candesartan did not significantly influence MAP or glomerular filtration rate, whereas filtration fraction was reduced by 27% +/- 5% vs. baseline (P < 0.05 vs. LPS-saline). In conclusion, candesartan, in a dose that did not significantly decrease MAP, caused renal vasodilation and markedly improved RBF and intrarenal P(O2) in endotoxemic rats. These findings suggest renoprotective effects of candesartan in sepsis.
|
|
| 25. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
N-acetylcysteine attenuates kidney injury in rats subjected to renal ischaemia-reperfusion
- 2006
-
Ingår i: Nephrol Dial Transplant. - : Oxford University Press (OUP). - 0931-0509. ; 21:5, s. 1240-7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the present study is to examine the effects of N-acetylcysteine (NAC), a thiol-containing anti-oxidant, on renal function and morphology, and biomarkers of oxidative stress, in rats subjected to renal ischaemia-reperfusion (IR). METHODS: Sprague-Dawley rats underwent unilateral nephrectomy and either contralateral renal IR (40 min of renal arterial clamping), or sham manipulation. Treatment groups were: (1) IR-Saline, (2) IR-NAC, (3) Sham-Saline and (4) Sham-NAC. The N-acetylcysteine was administered in a dose of 200 mg/kg intraperitoneally at 24, 12 and 2 h before, and 24, 48 and 72 h after, renal IR. Plasma creatinine was measured on days 1, 3 and 7 after IR, and kidney histology was assessed on day 7. In separate groups of animals we measured renal levels of the anti-oxidant glutathione, markers of systemic oxidative stress (plasma ascorbyl radical, urinary 8-iso-prostaglandin F2alpha), and glomerular filtration rate (GFR) by 51Cr-EDTA clearance, on day 1 after renal IR. RESULTS: Treatment with NAC ameliorated the decline in GFR and reduced hyperkalaemia on day 1 (P<0.05), lowered plasma creatinine levels on days 1 and 3 (P<0.05), and decreased renal interstitial inflammation on day 7 (P<0.05), after renal IR. Kidney glutathione levels decreased significantly in group IR-Saline in response to IR (P<0.05), but were completely repleted in group IR-NAC. Groups with renal IR injury and acute renal failure showed increased plasma ascorbyl radical levels, and elevated urinary 8-iso-prostaglandin F2alpha excretion, compared with sham (P<0.05). N-acetylcysteine treatment reduced plasma ascorbyl concentrations 24 h after renal IR (P<0.05), but had no effect on the rate of urinary 8-iso-prostaglandin F2alpha excretion. CONCLUSIONS: N-acetylcysteine improves kidney function, and reduces renal interstitial inflammation, in rats subjected to renal IR. These effects were associated with increased renal glutathione levels, and decreased plasma ascorbyl concentrations, suggesting that NAC attenuates renal and systemic oxidative stress in this model.
|
|
| 26. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Role of endothelin ET(A) and ET(B) receptor subtypes in the regulation of intrarenal blood flow and oxygen tension in rats
- 2008
-
Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 35:10, s. 1227-32
-
Tidskriftsartikel (refereegranskat)abstract
- 1. The aim of the present study was to investigate the role of endothelin ET(A) and ET(B) receptors in the regulation of intrarenal blood flow and oxygen tension in normotensive Sprague-Dawley rats. 2. Thiobutabarbital anaesthetized rats were divided into four groups (n = 6-9 per group): (i) saline (4 mL/kg per h); (ii) BQ123; (iii) BQ788; and (iv) BQ123 + BQ788. After baseline measurements, the ET(A) receptor antagonist BQ-123 (30 nmol/kg per min, i.v.) and/or the ET(B) receptor antagonist BQ-788 (30 nmol/kg per min, i.v.), was administered for a period of 60 min. Total renal blood flow (RBF), cortical and outer medullary perfusion (laser-Doppler flowmetry) and Po(2) (Clark-type microelectrodes) were analysed throughout. 3. At baseline, there were no significant differences between groups in mean arterial pressure (MAP), RBF, cortical and outer medullary perfusion and Po(2). Infusion of BQ-788 reduced RBF, cortical perfusion and outer medullary Po(2) (P < 0.05) and increased renal vascular resistance (P < 0.05) compared with saline-treated and BQ123 + BQ788-infused groups. BQ-123 and coinfusion of BQ-123 + BQ-788 increased outer medullary perfusion compared with the saline-treated group (P < 0.05) without significantly affecting outer medullary Po(2) and MAP. Neither selective nor combined ET(A) and ET(B) receptor antagonism significantly affected renal cortical Po(2). 4. In conclusion, in normotensive rats, ET(B) receptor antagonism caused renal vasoconstriction and reduced RBF and cortical perfusion. Furthermore, ET(B) receptor antagonism decreased outer medullary Po(2). These effects were mediated by ET(A) receptor activation and are not due to a lack of ET(B) receptor activation per se. Finally, BQ-123 increased renal outer medullary perfusion, suggesting a tonic vasoconstrictor effect of ET(A) receptors in the medulla of normotensive rats.
|
|
| 27. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Thrombin inhibition with melagatran does not attenuate renal ischaemia-reperfusion injury in rats.
- 2007
-
Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 0931-0509. ; 22:8, s. 2149-55
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Renal ischaemia-reperfusion (IR) is associated with activation of the coagulation system and inflammation within the kidney. The aim of the present study was to examine the effects of selective thrombin inhibition with melagatran on kidney morphology and function in rats subjected to renal IR. METHODS: Sprague-Dawley rats underwent renal IR (35 min of bilateral renal arterial clamping), or sham surgery. Treatment groups were: (i) IR-Saline, (ii) IR-Melagatran, (iii) Sham-Saline, and (iv) Sham-Melagatran. Twenty minutes prior to renal IR, the rats were administered a bolus dose of saline vehicle or melagatran [0.5 mumol/kg, subcutaneously (s.c.)] followed by a continuous infusion throughout (0.08 micromol/kg/h, s.c.). Forty-eight hours after IR, renal function was assessed in anaesthetized animals and kidney histology was analysed semi-quantitatively. RESULTS: Rats in group IR-Saline showed an approximate 85% reduction in glomerular filtration rate, 5-fold increases in fractional urinary excretion rates of sodium, potassium and water, and marked renal histological abnormalities, compared with sham (P < 0.05). Renal histopathological changes in the cortex and outer medulla were characterized by tubular necrosis and atrophy, tubular cast formation and interstitial inflammation. In addition, there was significant vascular congestion in the inner stripe of the outer medullary zone. Melagatran treatment had no significant effects on any of the abnormalities in kidney morphology or function in rats subjected to renal IR. Plasma melagatran concentrations were within a range known to exert significant antithrombotic effects, throughout the study period. CONCLUSIONS: Thrombin inhibition with melagatran did not ameliorate abnormalities in kidney morphology or function 48 h after renal IR. These results indicate that melagatran is not renoprotective in rats subjected to renal IR.
|
|
| 28. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
-
Urotensin II receptor antagonism does not improve renal hemodynamics or function in rats with endotoxin-induced acute kidney injury.
- 2010
-
Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 37:12, s. 1170-1175
-
Tidskriftsartikel (refereegranskat)abstract
- 1.Urotensin II (U-II) is a vasoactive peptide that influences renal hemodynamics and kidney function. The aim was to examine the effects of the selective U-II receptor antagonist urantide, on renal hemodynamics, oxygenation and function in endotoxemic rats. 2.Endotoxemia was induced in Sprague-Dawley rats by an intraperitoneal dose of lipopolysaccharide (LPS; E Coli O127:B8, 7.5 mg/kg). At 16 h after endotoxin administration, renal clearance experiments were performed in thiobutabarbital anesthetized rats. Groups (1) sham-saline, (2) sham-urantide, (3) LPS-saline and (4) LPS-urantide, received isotonic saline, or urantide (0.2 mg/kg bolus intravenously, followed by an infusion of 1.2 mg/kg/h throughout), after baseline measurements. Kidney function, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (Clark-type microelectrodes) were analyzed during 2 h of drug administration. 3.At baseline, endotoxemic rats showed approximate 50% reductions in glomerular filtration rate (GFR) and RBF (p<0.05), a decline in cortical and outer medullary perfusion and pO(2) (p<0.05), and a significant increase in mean arterial pressure (MAP; p<0.05), compared to saline-injected controls. In sham animals, urantide in a dose that did not significantly influence MAP or RBF, increased GFR (p<0.05 time x treatment interaction) and filtration fraction (p<0.05 treatment effect). However, urantide had no statistically significant effects on any of the investigated variables in endotoxemic rats. 4.These findings indicate that U-II, via the UT receptor, does not contribute to abnormalities in renal hemodynamics and function in endotoxemic rats.
|
|
| 29. |
- Nowakowska-Fortuna, Elzbieta, et al.
(författare)
-
Brain natriuretic peptides in atherosclerotic renal artery stenosis and effects of renal angioplasty
- 2013
-
Ingår i: Kidney and Blood Pressure Research. - : S. Karger AG. - 1420-4096 .- 1423-0143. ; 37:6, s. 657-66
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We hypothesized that plasma levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) would be elevated, and adiponectin concentrations reduced, in patients with atherosclerotic renal artery stenosis (ARAS) and that BNPs might be used to identify patients who would benefit from percutaneous transluminal renal angioplasty (PTRA). Methods: Data were collected before renal angiography in 91 patients with hypertension and suspected ARAS (significant ARAS; n=47, and non-RAS; n=44) and in 20 healthy controls (C). In ARAS patients analyses were repeated four weeks after PTRA. Results: Ambulatory systolic blood pressure (ASBP) was significantly elevated in the ARAS group vs. both C and non-RAS groups. Baseline plasma BNP and NT-proBNP levels were significantly elevated, and adiponectin concentrations reduced, in the ARAS group vs. C but not vs. the non-RAS group. One month after PTRA, ASBP was reduced vs. baseline (149+/-16 to 139+/-15 mm p<0.01). Brain natriuretic peptides were not significantly affected by PTRA. Conclusions: Patients with ARAS showed elevated of BNP and NT-proBNP concentrations, and reduced levels of adiponectin, compared to healthy controls but not vs. hypertensive individuals without RAS. Our data do no support the use of BNP analyses in the identification of ARAS patients who will have a beneficial blood pressure response to PTRA. (c) 2014 S. Karger AG, Basel.
|
|
| 30. |
- Nowakowska-Fortuna, Elzbieta, et al.
(författare)
-
Lipoprotein abnormalities in patients with atherosclerotic renovascular disease.
- 2011
-
Ingår i: Kidney & blood pressure research. - : S. Karger AG. - 1423-0143 .- 1420-4096. ; 34:5, s. 311-9
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with atherosclerotic renovascular disease (ARVD) have a high risk of cardiovascular death. The primary aim was to characterize abnormalities in apolipoprotein (Apo)-defined lipoprotein (Lp) subclasses in patients with ARVD.
|
|
| 31. |
- Rippe, C., et al.
(författare)
-
Targeting transcriptional control of soluble guanylyl cyclase via NOTCH for prevention of cardiovascular disease
- 2019
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 225:1
-
Tidskriftsartikel (refereegranskat)abstract
- Soluble guanylyl cyclase (sGC) is an effector enzyme of nitric oxide (NO). Recent work has unravelled how levels of this enzyme are controlled, and highlighted a role in vascular disease. We provide a timely summary of available knowledge on transcriptional regulation of sGC, including influences from the NOTCH signalling pathway and genetic variants. It is speculated that hypertension-induced repression of sGC starts a vicious circle that can be initiated by periods of stress, diet or genetic factors, and a key tenet is that reduction in sGC further raises blood pressure. The idea that dysregulation of sGC contributes to syndromes caused by defective NOTCH signalling is advanced, and we discuss drug repositioning for vascular disease prevention. The advantage of targeting sGC expression rather than activity is also considered. It is argued that transcriptional inputs on sGC arise from interactions with other cells, the extracellular matrix and microRNAs (miRNAs), and concluded that the promise of sGC as a target for prevention of cardiovascular disease has increased in recent time.
|
|
| 32. |
- Saeed, Aso, 1971, et al.
(författare)
-
Accuracy of colour duplex sonography for the diagnosis of renal artery stenosis.
- 2009
-
Ingår i: Journal of hypertension. - 1473-5598. ; 27:8, s. 1690-6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the diagnostic value of novel velocimetric colour duplex sonography indices in the screening of renal artery stenosis (RAS). METHODS: We performed a retrospective analysis of all consecutively studied patients at our centre with suspected RAS, and a colour duplex sonography carried out at less than 4 months (mean 34 days) before renal angiography during a 6-year period (2002-2007). A significant RAS was defined as an at least 60% stenosis on angiography or a transstenotic mean arterial pressure gradient of at least 10 mmHg or both. RESULTS: In a total of 169 patients, 111 stenotic and 206 nonstenotic kidneys were examined. The sensitivity and specificity for acceleration of blood flow in early systole (ACCmax) were 85 and 75%, respectively, and for the acceleration index (ACCmax/peak systolic velocity, AImax) 83 and 79%, respectively. Corresponding values in patients with estimated glomerular filtration rate of less than 30 ml/min/1.73 m2 were 90 and 73% (for ACCmax) and 74 and 88% (for AImax). In addition, the transstenotic mean arterial pressure gradient showed a significant, though weak, negative correlation to ACCmax (r = -0.26, P = 0.02) and AImax (r = -0.29, P = 0.01) in stenotic kidneys. CONCLUSION: ACCmax and AImax provide similar, good diagnostic accuracy in the detection of a haemodynamically significant RAS, even in patients with markedly reduced glomerular filtration rate. Presumably, the lack of superiority of the novel index AImax could be explained by a highly homogenous methodological approach in the present single-centre study.
|
|
| 33. |
|
|
| 34. |
- Saeed, Aso, 1971, et al.
(författare)
-
Effects of Endothelin Receptor Antagonists on Renal Hemodynamics in Angiotensin II-Infused Rats on High NaCl Intake
- 2012
-
Ingår i: Kidney & Blood Pressure Research. - : S. Karger AG. - 1420-4096 .- 1423-0143. ; 36:1, s. 258-267
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim was to investigate effects of selective endothelin (ET) receptor antagonists on renal hemodynamics and dynamic renal blood flow autoregulation (RBFA) in angiotensin II (Ang II)-infused rats on a high NaCl intake. Methods: Sprague-Dawley rats received Ang II (250 ng/kg/min, s.c.) and an 8 % NaCl diet for 14 days after which renal clearance experiments were performed. After baseline measurements animals were administered either: (a) saline vehicle; (b) ETA receptor antagonist BQ-123 (30 nmol/kg/min); (c) ETB receptor antagonist BQ-788 (30 nmol/kg/min); or (d) BQ-123 + BQ-788, for six consecutive 20-minute clearance periods. Results: BQ-123 reduced arterial pressure (AP) and selectively increased outer medullary perfusion versus vehicle (p<0.05). These effects were attenuated or abolished by combined BQ-123 and BQ-788. BQ-788 reduced renal blood flow and increased renovascular resistance (p<0.05). Ang II-infused rats on high NaCl intake showed abnormalities in dynamic RBFA characterized by an impaired myogenic response that were not significantly affected by ET receptor antagonists. Conclusion: In hypertensive Ang II-infused rats on a high-NaCl intake selective ETA antagonism with BQ-123 reduced AP and specifically increased OM perfusion and these effects were dependent on intact ETB receptor stimulation. Furthermore, ET receptor antagonists did not attenuate abnormalities in dynamic RBFA
|
|
| 35. |
- Saeed, Aso, 1971, et al.
(författare)
-
High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure
- 2014
-
Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 306:6
-
Tidskriftsartikel (refereegranskat)abstract
- This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous BRS was reduced by similar to 50% in ACRF animals. High-NaCl diet significantly increased transfer function fractional gain values between arterial pressure and RBF in the frequency range of the myogenic response (0.06-0.09 Hz) only in ACRF animals (0.3 +/- 4.0 vs. -4.4 +/- 3.8 dB; P < 0.05). Similarly, a high-NaCl diet significantly increased SAPV in the low-frequency range only in ACRF animals. To conclude, a 2-wk period of a high-NaCl diet in ACRF rats significantly impaired dynamic RBFA in the frequency range of the myogenic response and increased SAPV in the low-frequency range. These abnormalities may increase the susceptibility to hypertensive end-organ injury and progressive renal failure by facilitating pressure transmission to the microvasculature.
|
|
| 36. |
- Saeed, Aso, 1971, et al.
(författare)
-
High NaCl intake impairs dynamic autoregulation of renal blood flow in angiotensin II-infused rats.
- 2010
-
Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 299:5
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate dynamic autoregulation of renal blood flow (RBF) in angiotensin II (Ang II)-infused rats and the influence of high NaCl intake. Sprague-Dawley rats received Ang II (250 ng/kg/min, s.c.), or saline vehicle (Sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats (n=8-10 per group) were either on a normal (NNa, 0.4 % NaCl) or high (HNa, 8 % NaCl) NaCl diet. Separate groups were treated with Tempol (1 M in drinking water). Transfer function (TF) analysis from arterial pressure to RBF in the frequency domain was used to examine the myogenic response (MR, 0.06-0.09 Hz) and the tubuloglomerular feedback mechanism (TGF, 0.03-0.06 Hz). Mean arterial pressure was elevated in Ang II-infused rats compared to sham groups (p<0.05). RBF in Ang II HNa was reduced vs. Sham NNa and Sham HNa (6.0+/-0.3 vs. 7.9+/-0.3 and 9.1+/-0.3 ml/min/gKW, p<0.05). TF gain in Ang II HNa was significantly elevated in the frequency range of the MR (1.26+/-0.50 dB, p<0.05 vs. all other groups) and in the frequency range of the TGF (-0.02+/-0.50 dB, p<0.05 vs. Sham NNa and Sham HNa). Gain values in the frequency range of the MR and TGF were significantly reduced by Tempol in Ang II-infused rats on HNa diet. In summary, the MR and TGF components of RBF autoregulation were impaired in Ang II HNa and these abnormalities were attenuated by Tempol suggesting a pathogenetic role for superoxide in the impaired RBF autoregulatory response.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
