Evidence for endothelin-induced renal vasoconstriction independent of ETA receptor activation

1993 ◽  
Vol 264 (1) ◽  
pp. R222-R226 ◽  
Author(s):  
D. M. Pollock ◽  
T. J. Opgenorth
Keyword(s):  
Glomerular Filtration Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Renal Vascular Resistance ◽  
Renal Vascular

Experiments were designed to examine the role of endothelin (ET) receptors, specifically ETA receptors, in mediating the renal vasoconstrictor effects of ET-1 in anesthetized Sprague-Dawley rats. Intravenous infusion of ET-1 at 25 pmol.kg-1 x min-1 for 60 min produced a significant increase in mean arterial pressure (20 +/- 7%) and decreases in renal plasma flow (-60 +/- 6%) and glomerular filtration rate (-47 +/- 6%). Renal vascular resistance was significantly increased from 17 +/- 1 mmHg.ml-1 x min.g kidney wt during control period to 54 +/- 11 mmHg.ml-1 x min.g kidney wt during the experimental period. A second group of rats was infused with both ET-1 and the specific ETA receptor antagonist BQ-123 (0.1 mg.kg-1 x min-1). ET-1-induced increases in mean arterial pressure were completely blocked by BQ-123 (the average change was -7 +/- 4%). However, the renal vasoconstrictor effects of ET-1 were not affected by the antagonist, since renal plasma flow and glomerular filtration rate were again significantly reduced (-54 +/- 4 and -56 +/- 6%, respectively). Once again, renal vascular resistance was significantly increased from 16 +/- 2 mmHg.ml-1 x min.g kidney wt during the control period to 33 +/- 5 mmHg.ml-1 x min.g kidney wt during the experimental period. In a third group, infusion of BQ-123 alone produced a significant decline in mean arterial pressure (-13 +/- 2%), with no significant changes in renal plasma flow or glomerular filtration rate, thus producing a significant decrease in renal vascular resistance (15 +/- 1 vs. 11 +/- 2 mmHg.ml-1 x min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the enantiomers of a new dihydropyridine derivative, S12968 and S12967, on renal functions in rats

1993 ◽  
Vol 71 (10-11) ◽  
pp. 848-853
Author(s):  
José M. López-Novoa ◽  
Inmaculada Montañés
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Hypotensive Effect

The aim of this study was to evaluate the effects of the two enantiomers of a new dihydropyridine, S12967 and S12968, on rat renal function. Male Wistar rats were injected intravenously with saline, S12967, or S12968 (0.1, 0.3, or 1 mg/kg body weight). Urinary flow, glomerular filtration rate, renal plasma flow, urinary sodium, potassium, and calcium excretions, mean arterial pressure, and renal vascular resistance were determined before and every 30 min up to 180 min after administration of the tested substance. The levogyre enantiomer S12968, at a dose of 0.3 mg/kg, induced a 4-fold increase in urinary sodium excretion, without significant or with minor changes in glomerular filtration rate, renal plasma flow, or renal blood flow. The hypotensive effect was small and nonsignificant. At 1 mg/kg, S12968 caused a profound hypotensive effect that impaired the renal function, induced marked oliguria, and decreased glomerular filtration rate and renal blood flow to almost negligible values. The dextrogyre enantiomer S12967 had much less effect on renal function. These data showing specific stereoselective renal effects are in agreement with pharmacological studies that have demonstrated that S12968 possesses a higher affinity for the dihydropyridine-binding site than its dextrogyre enantiomer, S12967.Key words: Ca channel antagonists, dihydropyridine, glomerular filtration rate, renal blood flow, natriuresis, mean arterial pressure.

Renal autoregulation: perspectives from whole kidney and single nephron studies

1978 ◽  
Vol 234 (5) ◽  
pp. F357-F370 ◽  
Author(s):  
L. G. Navar
Keyword(s):  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Distal Nephron ◽  
Renal Autoregulation ◽  
Single Nephron ◽  
Renal Vascular

The phenomenon of renal autoregulation is often thought to relate only to the manner in which the kidney responds to changes in arterial pressure. This review presents a more comprehensive description of the process based on the intrinsic renal vascular responses to changes in arterial pressure, venous pressure, ureteral pressure, and plasma colloid osmotic pressure. Regulation of glomerular filtration rate (GFR), or some function thereof, is the feature most consistently observed. More specifically, in response to external manipulations that change GFR, autonomous changes in renal vascular resistance tend to return GFR back towards normal. The bulk of the evidence suggests that the requisite renal vascular resistance alterations occur predominately at preglomerular segments. Most of the whole kidney autoregulatory responses can be explained on the basis of the distal tubule-glomerular feedback hypothesis, thought to be mediated by the macula densa-juxtaglomerular complex, which states that increases in distal volume delivery lead to increases in afferent arteriolar resistance while reduced distal delivery leads to afferent arteriolar dilation. Micropuncture data have demonstrated that interruption of distal volume delivery prevents single nephrons from autoregulating GFR and glomerular pressure. Also, single nephron glomerular filtration rate (SNGFR) based on proximal collections is higher than SNGFR measured by distal collections or with an indicator-dilution technique. Studies utilized direct microperfusion of the distal nephron from a late proximal tubule site have demonstrated that SNGFR and glomerular pressure decrease in response to increases in distal nephron perfusion rate. Although experiments in rats have been interpreted as indicating that distal chloride concentration and/or reabsorption most likely mediate the feedback responses, recent studies in dogs have demonstrated that feedback responses can be consistently obtained with nonelectrolyte perfusion solutions. These latter studies suggest that the feedback response may be sensitive to some function of total solute delivery or concentration. At present, there is no clear understanding of the intracellular events that link the compositional alterations occurring within the early distal tubule to the final effector system.

scholarly journals Individual renal hemodymamic response to chronic angiotensin II receptor bloc­kade and the influence on the renin-angiotensin system gene polymorphisms

2010 ◽  
Vol 63 (9-10) ◽  
pp. 630-637
Author(s):  
Tamara Dragovic ◽  
Boris Ajdinovic ◽  
Vesna Ilic ◽  
Zvonko Magic ◽  
Zoran Andjelkovic ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Filtration Fraction ◽  
Renal Vascular ◽  
Losartan Treatment

Introduction. Our study was aimed at determining whether the polymorphism of genes for different components of the renin-angiotensin-aldosterone system could influence the renal hemodynamic response to losartan treatment. Material and method. The study included 35 patients with type 1 diabetes mellitus and persistent albuminuria, genotyped for the 1166 A/C polymorphism gene for the angiotensin II type 1 receptor and I/D polymorphism of the angiotensin-converting enzyme gene. The participants were divided into groups according to the combinations of A or C allele: AA, AC, CC; and according to the combinations of I or D allele: II, ID and DD genotype. The patients received losartan therapy for 12 weeks. The renal hemodynamic measurements were determined at baseline and after the examination period. Results. Losartan therapy significantly reduced the filtration fraction from the baseline by 0.018?0.024 (p=0.012) only in the AC genotype. The glomerular filtration rate remained unchanged in all genotype groups. A significant increase in the effective renal plasma flow was obtained only in AC genotype (544?88 vs 575?90ml/min; p=0.02), while significant reductions in the renal vascular resistance were found in AA group (115?25 vs 95?21 mmHgx1-1xmin-1; p=0.001) and in AC group (118?30 vs 101?28 mmHgx1-1xmin-1; p=0.001). A significant reduction of the glomerular filtration rate by 8?10 ml/min was obtained only in the DD genotype (p=0.016), and only the DD genotype achieved a significant reduction of the filtration fraction by 0.019?0,022 (p=0.008). The most pronounced increase of the effective renal plasma flow was found only in the ID genotype (536 ?75 vs 591?63 ml/min; p=0.01). The reduction of the renal vascular resistance was independent of ACE gene polymorphism. Conclusion. Our study shows that individual renal vascular response to losartan treatment in diabetic patients with persistent albuminuria, could be influenced by genetic polymorphisms.

Combined prenatal and postnatal protein restriction influences adult kidney structure, function, and arterial pressure

2007 ◽  
Vol 292 (1) ◽  
pp. R462-R469 ◽  
Author(s):  
Chantal C. Hoppe ◽  
Roger G. Evans ◽  
Karen M. Moritz ◽  
Luise A. Cullen-McEwen ◽  
Sharyn M. Fitzgerald ◽  
...  
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Salt Intake ◽  
Renal Plasma Flow ◽  
Protein Restriction ◽  
Nephron Number

The effects of prenatal protein restriction on adult renal and cardiovascular function have been studied in considerable detail. However, little is known about the effects of life-long protein restriction, a common condition in the developing world. Therefore, we determined in rats the effects of combined pre- and postnatal protein restriction on adult arterial pressure and renal function and responses to increased dietary sodium. Nephron number was also determined. Male Sprague-Dawley rats were born to mothers fed a low [8% (wt/wt), LP] or normal [20% (wt/wt), NP] isocaloric protein diet throughout pregnancy and maintained on these diets after birth. At postnatal day 135, nephron number, mean arterial pressure (MAP), and renal function were determined. A high-NaCl [8.0% (wt/wt), high-salt] diet was fed to a subset of rats from weaning. MAP was less in LP than in NP rats (120 ± 2 vs. 128 ± 2 mmHg, P < 0.05) and was not significantly altered by increased salt intake. Nephron number was 31% less in LP than in NP rats ( P < 0.001). The volume of individual glomeruli was also less in LP than in NP rats, as were calculated effective renal plasma flow and glomerular filtration rate. Glomerular filtration rate, but not effective renal plasma flow, appeared to be increased by high salt intake, particularly in LP rats. In conclusion, protein restriction induced a severe nephron deficit, but MAP was lower, rather than higher, in protein-restricted than in control rats in adulthood. These findings indicate that the postnatal environment plays a key role in determining the outcomes of developmental programming.

Interaction between angiotensin II and nitric oxide in control of renal hemodynamics in conscious dogs

1994 ◽  
Vol 267 (6) ◽  
pp. R1472-R1478 ◽  
Author(s):  
A. M. Alberola ◽  
F. J. Salazar ◽  
T. Nakamura ◽  
J. P. Granger
Keyword(s):  
Nitric Oxide ◽  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Nitric Oxide Synthesis ◽  
Afferent Arterioles ◽  
Renal Vascular

Recent in vitro studies have provided evidence that the vasoconstrictor actions of angiotensin II on afferent arterioles are enhanced by nitric oxide synthesis inhibition. Although these studies suggest that nitric oxide may play a role in protecting the afferent arterioles from angiotensin II-induced vasoconstriction, the importance of this interaction in the regulation of glomerular filtration rate and renal blood flow in the intact, conscious animal is not known. The objective of the present study was to determine the role of nitric oxide in modulating the renal hemodynamic and excretory effects of angiotensin II. Angiotensin II was infused at rates of 0.5, 1.0, and 2.0 micrograms.kg-1.min-1 intrarenally in conscious, chronically instrumented dogs in both the presence and absence of nitric oxide synthesis inhibition by continuous intrarenal infusion of NG-nitro-L-arginine methyl ester (3 micrograms.kg-1.min-1). At a dose of 0.5 micrograms.kg-1.min-1, angiotensin II decreased renal plasma flow by 19%, while having no effect on glomerular filtration rate in control dogs. In contrast, angiotensin II decreased renal plasma flow by 54%, glomerular filtration rate by 40%, and increased renal vascular resistance by 125% in the presence of intrarenal nitric oxide synthesis blockade. At doses of 1.0 and 2.0 micrograms.kg-1.min-1, angiotensin II reduced renal plasma flow by 36 and 45%, glomerular filtration rate by 17 and 23%, and increased renal vascular resistance by 80 and 120%, respectively, in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Renal Function Testing by External Double Isotope Monitoring Technique

1971 ◽  
Vol 10 (01) ◽  
pp. 16-24
Author(s):  
J. Fog Pedersen ◽  
M. Fog Pedersen ◽  
Paul Madsen
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Effective Renal Plasma Flow ◽  
Advantages And Disadvantages

SummaryAn accurate catheter-free technique for clinical determination simultaneouslyof glomerular filtration rate and effective renal plasma flow by means of radioisotopes has been developed. The renal function is estimated by the amount of radioisotopes necessary to maintain a constant concentration in the patient’s blood. The infusion pumps are steered by a feedback system, the pumps being automatically turned on when the radiation measured over the patient’s head falls below a certain preset level and turned off when this level is again readied. 131I-iodopyracet was used for the estimation of effective renal plasma flow and125I-iothalamate estimation of the glomerular filtration rate. These clearances were compared to the conventional bladder clearances and good correlation was found between these two clearance methods (correlation coefficients 0.97 and.90 respectively). The advantages and disadvantages of this new clearance technique are discussed.

Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat

1991 ◽  
Vol 81 (2) ◽  
pp. 271-279 ◽  
Author(s):  
P. G. McNally ◽  
F. Baker ◽  
N. Mistry ◽  
J. Walls ◽  
J. Feehally
Keyword(s):  
Body Weight ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Cyclosporin A ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Denervation ◽  
Renal Plasma Flow ◽  
Spontaneously Hypertensive

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 ± 22 ng/ml, means ± sem). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 ± 0.04 versus 0.70 ± 0.06 ml min−1 100 g body weight, P < 0.02) and effective renal plasma flow (1.94 ± 0.10 versus 1.38 ± 0.13, P < 0.01), and increased renal vascular resistance {(20.2 ± 1.8) × 104 versus (31.6 ± 3.3) × 104 kPa l−1 s [(20.2 ± 1.8) × 103 versus (31.6 ± 3.3) × 103 dyn s cm−5], P < 0.02} and mean arterial pressure (146.7 ± 6.7 versus 167.3 ± 2.9 mmHg, P < 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.

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