Verapamil Alters the Relationship Between Renal Perfusion Pressure and Glomerular Filtration Rate and Renin Release

The present study was designed to determine whether atrial appendectomy would decrease the sodium excretion associated with pressor doses of arginine vasopressin (AVP) infusion in rats by decreasing circulating levels of atrial natriuretic factor (ANF). Ten to 21 days after either sham (n = 9) or bilateral atrial appendectomy (n = 13) AVP (19 ng.kg-1.min-1) was infused for 90 min in anesthetized Sprague-Dawley rats. Atrial appendectomy decreased circulating ANF levels from 469 +/- 70 pg/ml in sham-operated animals to 259 +/- 50 pg/ml (P less than 0.05) in atrial-appendectomized animals after 90 min of AVP infusion. Despite a reduction in circulating levels of ANF, sodium excretion, potassium excretion, and urine flow increased and were not affected by bilateral atrial appendectomy. Glomerular filtration rate and mean arterial pressure significantly increased in both groups of rats. The present study supports non-ANF factors such as increases in renal perfusion pressure and/or glomerular filtration rate as potential mechanisms in AVP-induced natriuresis.

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Renal autoregulation of blood flow and filtration rate in the rabbit

AJP Renal Physiology ◽

10.1152/ajprenal.1979.237.6.f479 ◽

1979 ◽

Vol 237 (6) ◽

pp. F479-F482 ◽

Cited By ~ 3

Author(s):

C. E. Ott ◽

R. C. Vari

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Renal Blood Flow ◽

Filtration Rate ◽

Pressure Range ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Rabbit Kidney ◽

Renal Perfusion Pressure

Electromagnetic flow techniques and inulin clearance were used to determine the autoregulatory capabilities of the rabbit kidney in vivo. Renal blood flow was measured in 13 animals over a renal perfusion pressure range of 40–110 mmHg. Normal renal blood flow averaged 3.2 +/- 0.3 ml.min-1.g kidney-1 and was efficiently autoregulated above a renal artery pressure of 75 mmHg. For every 10 mmHg renal pressure change above 75 mmHg renal blood flow changed only 0.96%. Renal perfusion pressure was reduced from 102 +/- 3 to 74 +/- 2 mmHg in six animals. Over this pressure range glomerular filtration rate was not significantly decreased and averaged 4.2 +/- 0.5 ml/min at high pressure compared to 4.0 +/- 0.5 ml/min at low perfusion pressure. Results show that the rabbit kidney autoregulates renal blood flow and glomerular filtration rate efficiently above 75 mmHg. This range of autoregulation compares well with the autoregulatory range of the dog. The results also show that in the autoregulatory range the rabbit and the rat appear to autoregulate with equal efficiency but that the rabbit kidney begins to autoregulate at a low perfusion pressure than the average of approximately 100 mmHg usually found in the rat.

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Glomerular filtration dynamics during renal vasodilation with acetylcholine in the dog

AJP Renal Physiology ◽

10.1152/ajprenal.1983.244.6.f606 ◽

1983 ◽

Vol 244 (6) ◽

pp. F606-F611 ◽

Cited By ~ 4

Author(s):

C. E. Thomas ◽

C. E. Ott ◽

P. D. Bell ◽

F. G. Knox ◽

L. G. Navar

Keyword(s):

Glomerular Filtration Rate ◽

Proximal Tubule ◽

Glomerular Filtration ◽

Filtration Rate ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Renal Perfusion Pressure ◽

Effective Filtration Pressure ◽

Single Nephron ◽

Flow Dependency

The reason for the failure of glomerular filtration rate (GFR) to exhibit plasma flow dependency during pharmacologic vasodilation remains unclear although it has been suggested on the basis of experiments in rats that vasodilators may lead to a reduction in the glomerular filtration coefficient (Kf). To evaluate the applicability of this hypothesis to the dog, the effects of vasodilation with acetylcholine on glomerular dynamics and Kf were evaluated in two groups of dogs. One group (n = 19) was studied at spontaneous arterial pressures to allow maximum vasodilation to occur. In the other group (n = 5), renal arterial pressure was reduced and maintained at approximately 89 mmHg. Glomerular filtration rate and single nephron glomerular filtration rate were not altered significantly during acetylcholine infusion in either of the two groups. Both whole kidney and superficial filtration fractions decreased significantly. At spontaneous arterial pressures, transglomerular hydrostatic pressure was not altered significantly because of equivalent increases in proximal tubule pressure and in glomerular pressure. In the dogs studied at reduced renal perfusion pressure, glomerular capillary pressure did not change, but proximal tubule pressure increased slightly. Average effective filtration pressures and Kf were not significantly altered during the infusion of acetylcholine either at spontaneous or reduced renal perfusion pressures. These observations indicate that Kf in the dog is not significantly decreased by acetylcholine and that GFR is not affected during infusion of this agent because the effective filtration pressure is not significantly altered.

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Autoregulation of renal blood flow and glomerular filtration rate in the pregnant rabbit

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.252.1.r69 ◽

1987 ◽

Vol 252 (1) ◽

pp. R69-R72 ◽

Cited By ~ 5

Author(s):

L. L. Woods ◽

H. L. Mizelle ◽

J. E. Hall

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Renal Blood Flow ◽

Filtration Rate ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Renal Perfusion Pressure ◽

Pregnant Rabbit ◽

In Pregnancy

Our purpose was to determine whether renal autoregulatory capability is retained in pregnancy despite the marked renal vasodilation that occurs at this time. Renal blood flow and glomerular filtration rate (GFR) were measured in anesthetized pregnant (22–27 days gestation) and nonpregnant rabbits during step reductions in renal perfusion pressure from control (100 +/- 3 mmHg) to 50 mmHg. Control renal blood flow and GFR were significantly higher in pregnant animals, averaging 65 +/- 5 and 13.1 +/- 1.1 ml/min, respectively, compared with 50 +/- 5 and 9.4 +/- 1.2 ml/min in nonpregnant rabbits. Filtration fraction was also significantly elevated in pregnant animals (0.33 +/- 0.02 vs. 0.27 +/- 0.01 in nonpregnant rabbits). During step reductions in renal perfusion pressure, renal blood flow was well autoregulated down to approximately 70 mmHg in both nonpregnant and pregnant animals, falling by only 9 +/- 4 and 12 +/- 5%, respectively. Likewise, GFR was also well autoregulated, falling by 10 +/- 2 and 8 +/- 3% in nonpregnant and pregnant animals, respectively, when perfusion pressure was reduced from 90 to 70 mmHg. These results suggest that renal autoregulation is preserved in pregnancy despite the fact that the renal circulation is already markedly vasodilated.

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Chronic Sodium-Potassium-ATPase Inhibition with Ouabain Impairs Renal Haemodynamics and Pressure Natriuresis in the Rat

Clinical Science ◽

10.1042/cs0910497 ◽

1996 ◽

Vol 91 (4) ◽

pp. 497-502 ◽

Cited By ~ 15

Author(s):

Toshiaki Kurashina ◽

Kent A. Kirchner ◽

Joey P. Granger ◽

Ami R. Patel

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Sodium Excretion ◽

Filtration Rate ◽

Perfusion Pressure ◽

Urinary Sodium Excretion ◽

Renal Perfusion ◽

Control Group ◽

Renal Perfusion Pressure

1. Chronic Na+,K+-ATPase inhibition with ouabain induces hypertension in the rat. To examine the role of the kidney in this process, the effect of changes in renal perfusion pressure on glomerular filtration rate, renal blood flow and urinary sodium excretion were determined in rats treated intraperitoneally with ouabain (27.8 μg day−1 kg−1 body weight) or vehicle for 6 weeks. 2. After ouabain administration, baseline mean arterial pressure was significantly higher (P < 0.05) in ouabain-treated rats (151 ± 2 mmHg; n = 9) than in control rats (116 ± 4 mmHg; n = 8). 3. At equivalent renal perfusion pressures, glomerular filtration rate was significantly lower (P < 0.05) in ouabain-treated rats compared with control rats. Glomerular filtration rate was 721 ± 73μl/min at 150 mmHg, and fell significantly to 322 ± 64 μl/min at 100 mmHg. In the control group, glomerular filtration rate was well autoregulated. The glomerular filtration rate autoregulatory index was calculated to determine the ability to maintain glomerular filtration rate during changes in renal perfusion pressure (0 reflects perfect autoregulation; >1 reflects the absence of autoregulation). This index was greater in the ouabain group than in the control group (1.54 ± 0.2 compared with 0.29 ± 0.2; P < 0.05). Renal blood flow showed a similar pattern. 4. Absolute urinary sodium excretion rate was less in ouabain-treated rats than in control rats at equivalent renal perfusion pressures. The slope of the relationship between absolute urinary sodium excretion rate and renal perfusion pressure was greater (P < 0.05) in the control group than in the ouabain group (309.1 ± 57.1 compared with 82.1 ± 14.8 μmol min−1 mmHg−1). 5. Thus, chronic inhibition of Na+,K+-ATPase induces less efficient autoregulation of glomerular filtration rate and renal blood flow as well as a rightward shift in the pressure natriuresis relationship, such that a 25–30 mmHg higher renal perfusion pressure is necessary to excrete any given sodium load. These abnormalities may contribute to the development and maintenance of hypertension in this model.

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Effect of Hypoxia and Hypercapnic Acidosis on Renal Autoregulation in the Dog: Role of Renal Nerves

Clinical Science ◽

10.1042/cs0650533 ◽

1983 ◽

Vol 65 (5) ◽

pp. 533-538 ◽

Cited By ~ 6

Author(s):

Robert J. Anderson ◽

Richard G. Pluss ◽

William T. Pluss ◽

Jon Bell ◽

Gary G. Zerbe

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Renal Blood Flow ◽

Filtration Rate ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Renal Nerves ◽

Hypercapnic Acidosis ◽

Renal Perfusion Pressure

1. Previous studies suggest that hypoxia and hypercapnic acidosis exert a renal nerve mediated adverse effect on renal haemodynamic function. We therefore examined the effect of hypoxia and hypercapnic acidosis on renal blood flow and glomerular filtration rate responses to lowering renal perfusion pressure from 125 to 75 mmHg in the anaesthetized dog. To study the role of renal nerves in these responses, paired innervated and denervated kidneys were studied in each animal. 2. Hypoxia (Po2 43 ± 3 mmHg) affected neither renal blood flow nor glomerular filtration rate responses to decreasing renal perfusion pressure. 3. Hypercapnic acidosis (Pco2 71 ±2 mmHg; pH 7.03 ± 0.01) significantly decreased both renal blood flow and glomerular filtration rate as renal perfusion pressure was lowered. This effect of hypercapnic acidosis could be abolished by renal denervation. 4. These findings suggest that hypercapnic acidosis results in renal nerve stimulation, which prevents the usual decrease in renal afferent arteriolar tone that occurs in response to lowering of renal perfusion pressure.

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Pressure-Diuresis-Natriuresis Response in Hyperthyroid and Hypothyroid Rats

Clinical Science ◽

10.1042/cs0870323 ◽

1994 ◽

Vol 87 (3) ◽

pp. 323-328 ◽

Cited By ~ 24

Author(s):

Félix Vargas ◽

Noemí M. Atucha ◽

J. Mario Sabio ◽

Tomás Quesada ◽

Joaquín García-Estañ

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Perfusion Pressure ◽

Normal Pressure ◽

Renal Perfusion ◽

Renal Perfusion Pressure ◽

Pressure Natriuresis ◽

Renal Responses ◽

Water And Sodium Excretion

1. Renal responses to changes in renal perfusion pressure were studied in anaesthetized hyperthyroid (thyroxine, 300 μg day−1 kg−1) and hypothyroid (methimazole, 0.03% via drinking water) rats to determine whether an abnormality in the pressure-diuresis-natriuresis phenomenon is involved in the resetting of kidney function in these disorders. 2. There were no significant differences between control and hypothyroid rats with respect to the relationships between renal perfusion pressure and absolute or fractional water and sodium excretion. However, in hyperthyroid rats the pressure-diuresis-natriuresis mechanism was impaired. 3. Renal blood flow and glomerular filtration rate were well autoregulated and there were no differences between control and hypothyroid rats at every level of renal perfusion pressure. A significantly lower glomerular filtration rate was observed in hyperthyroid rats when data were expressed per gram kidney weight, but glomerular filtration rate was similar to that of control rats when normalized by body weight. 4. The shift in the pressure-diuresis-natriuresis response of hyperthyroid rats is mainly due to an increase in tubular reabsorption. Blunting of the renal pressure-diuresis-natriuresis mechanism in hyperthyroid rats may represent the functional resetting of the kidney necessary for sustained hypertension. However, a normal pressure-natriuresis response was observed in hypothyroid rats, in which blood pressure was markedly reduced.

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Abstract 6277: Predictive Value of Estimated Glomerular Filtration Rate for Cardiovascular Events: The Treating to New Targets Study

Circulation ◽

10.1161/circ.118.suppl_18.s_1172-d ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

James Shepherd ◽

Chuan-Chuan Wun ◽

Daniel J Wilson ◽

Andrea L Zuckerman

Keyword(s):

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Cardiovascular Events ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Lipid Lowering ◽

Final Visit ◽

The Relationship ◽

Dose Dependent

We previously demonstrated a dose-dependent improvement in renal function and reduction in cardiovascular risk in TNT with intensive lipid lowering with atorvastatin (ATV) 80 mg vs 10 mg. This post hoc analysis examines the relationship between the observed improvement in estimated glomerular filtration rate (eGFR) and reduction of major cardiovascular events (MCVE). After 8 weeks open-label therapy with ATV 10 mg, 10,001 patients with CHD were randomized to double-blind therapy with either ATV 10 or 80 mg. Patients were followed for a median of 4.9 years for the occurrence of MCVEs (CHD death, nonfatal MI, and stroke). The relationship between change from baseline eGFR (using the MDRD equation) at the final visit prior to a MCVE and the risk of MCVE was assessed using a Cox proportional hazards model adjusting for baseline eGFR and other baseline characteristics. Of 9656 patients with complete renal data, 156 had a MCVE before follow-up eGFR assessment and were excluded. In the remaining 9500 patients, mean baseline eGFR was 65.3 mL/min/1.73 m 2 and mean change from baseline was 4.3 mL/min/1.73 m 2 . This represented a reduction in the risk of MCVE of 2.7% per mL increase in eGFR (HR 0.973, 95% CI 0.967– 0.980, P <0.0001). This association remained significant in patients with eGFR <60 and those with eGFR ≥60 mL/min/1.73 m 2 at baseline, with no significant interaction between eGFR change and baseline renal status ( P =0.98). A 5 mL/min on-treatment improvement in eGFR was associated with a 12.6% reduction in MCVE, while a 5 mL/min reduction was associated with a 14.4% increase in MCVE. Mean change from baseline eGFR was 3.5 mL/min/1.73 m 2 with ATV 10 mg and 5.2 mL/min/1.73 m 2 with ATV 80 mg, representing significant 9.3% and 12.4% reductions in risk, respectively. Analysis of interaction between treatment and eGFR change for prediction of MCVE demonstrated a stronger association between eGFR change and MCVE in the ATV 80 mg treatment group ( P =0.011). Improvement in eGFR was highly associated with a reduction in MCVE, irrespective of baseline renal function. This relationship was dose dependent. Improvement in eGFR may be a biomarker for the response to atorvastatin, and for the stabilization of atherosclerotic cardiovascular disease.

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