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.

Genetic co-segregation of renal haemodynamics and blood pressure in the spontaneously hypertensive rat

1988 ◽  
Vol 74 (1) ◽  
pp. 63-69 ◽  
Author(s):  
S. B. Harrap ◽  
A. E. Doyle
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Renin ◽  
Spontaneously Hypertensive

1. To determine the relevance of renal circulatory abnormalities found in the immature spontaneously hypertensive rat (SHR) to the genetic hypertensive process, glomerular filtration rate and renal blood flow were measured in conscious F2 rats, derived from crossbreeding SHR and normotensive Wistar–Kyoto rats (WKY), at 4, 11 and 16 weeks of age by determining the renal clearances of 51Cr-ethylenediaminetetra-acetate and 125I-hippuran respectively. Plasma renin activity was measured at 11 and 16 weeks of age. 2. Mean arterial pressure, glomerular filtration rate and renal blood flow increased between 4 and 11 weeks of age. Between 11 and 16 weeks the mean glomerular filtration rate and renal blood flow did not alter, although the mean arterial pressure rose significantly. At 11 weeks of age, during the developmental phase of hypertension, a significant negative correlation between mean arterial pressure and both glomerular filtration rate and renal blood flow was noted. However, by 16 weeks when the manifestations of genetic hypertension were more fully expressed, no correlation between mean arterial pressure and renal blood flow or glomerular filtration rate was observed. Plasma renin activity was negatively correlated with both glomerular filtration rate and renal blood flow, but the relationship was stronger at 11 than at 16 weeks of age. 3. These results suggest that the reduction in renal blood flow and glomerular filtration rate, found in immature SHR, is genetically linked to the hypertension and may be of primary pathogenetic importance. It is proposed that the increased renal vascular resistance in these young animals stimulates the rise of systemic arterial pressure which returns renal blood flow and glomerular filtration rate to normal.

Renal hemodynamics in conscious rats: effects of anesthesia, surgery, and recovery

1983 ◽  
Vol 245 (1) ◽  
pp. F67-F74 ◽  
Author(s):  
L. A. Walker ◽  
M. Buscemi-Bergin ◽  
M. Gellai
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Severe Depression ◽  
Renal Hemodynamics ◽  
Ether Anesthesia

The influence of barbiturate anesthesia and minor surgical incisions on renal function was assessed in trained, chronically catheterized rats. In addition, renal hemodynamic changes during recovery from ether anesthesia and surgery were examined. Administration of pentobarbital in the chronic animals was associated with a marked reduction in arterial pressure (108 +/- 5 vs. 85 +/- 2 mmHg, P less than 0.01), renal blood flow (8.28 +/- 0.50 vs. 6.20 +/- 0.53 ml X min-1 X 100 g body wt-1, P less than 0.01), and glomerular filtration rate (1.30 +/- 0.10 vs. 0.97 +/- 0.11 ml X min-1 X 100 g body wt-1, P less than 0.01). Responses to Inactin were essentially identical. Small skin incisions during barbiturate anesthesia caused blood pressure to rise, but did not significantly change renal function parameters from already reduced values. In rats studied 2 h after ether anesthesia and surgical placement of catheters, arterial pressure was elevated compared with the same rats studied 4-7 days later (127 +/- 3 vs. 109 +/- 3 mmHg, P less than 0.005). Renal blood flow (5.80 +/- 0.37 vs. 8.90 +/- 0.93 ml X min-1 X 100 g body wt-1, P less than 0.01) and glomerular filtration rate (0.81 +/- 0.07 vs. 1.05 +/- 0.08 ml X min-1 X 100 g body wt-1, P less than 0.001) were markedly depressed during the recovery from surgery. It is concluded that barbiturate anesthesia depresses renal function in rats. This impairment should be considered when interpreting experiments that must be performed under anesthesia. In addition, the "conscious" preparation commonly used for renal studies in rats, i.e., one involving experimentation 2-3 h after ether anesthesia and surgery, is associated with a severe depression of renal hemodynamics.

Renal actions of atrial natriuretic peptide on the postischemic kidney

1988 ◽  
Vol 66 (5) ◽  
pp. 601-607 ◽  
Author(s):  
Satoshi Akabane ◽  
Masahito Imanishi ◽  
Yohkazu Matsushima ◽  
Minoru Kawamura ◽  
Morio Kuramochi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Atrial Natriuretic Peptide ◽  
Renal Artery ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Natriuretic Peptide ◽  
Filtration Rate ◽  
Systemic Arterial Pressure

The objective of this study was to evaluate the renal actions of atrial natriuretic peptide (ANP) in the unilateral postischemic kidney of anesthetized dogs with a severe reduction in glomerular filtration rate. The dose of atrial natriuretic peptide (50 ng∙kg−1∙min−1) we gave did not alter the mean systemic arterial pressure, renal blood flow, and glomerular filtration rate in the normal kidney, as determined in foregoing studies. ANP was infused into the intrarenal artery continuously for 60 min after the release from 45 min of complete renal artery occlusion. In the vehicle-infused group, the glomerular filtration rate fell dramatically (6% of control), the renal blood flow decreased (60% of control), and the mean systemic arterial pressure tended to increase (136% of control). The urine flow rate and urinary excretion of sodium decreased significantly (25 and 25%, respectively) at 30 min after reflow in the postischemic period. Continuous renal artery infusion of ANP resulted in a marked increase in urine flow rate (246% of control) and the urinary excretion of sodium (286% of control). The administration of ANP led to an improvement in renal blood flow (99% of control) and glomerular filtration rate (40% of control), and attenuated the rise in mean systemic arterial pressure (109% of control), compared with findings in the vehicle-infused group. Plasma renin activity and prostaglandin E2 concentration in the renal venous blood were elevated after the release from complete renal artery occlusion in both groups. These results indicate that the vascular effects of ANP on the postischemic kidney were enhanced and that the peptide maintained the natriuretic effect.

Changes in renal function resulting from norepinephrine infusion

1962 ◽  
Vol 202 (5) ◽  
pp. 893-896 ◽  
Author(s):  
Jimmy B. Langston ◽  
Arthur C. Guyton ◽  
James H. DePoyster ◽  
George G. Armstrong
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Direct Effect ◽  
Infusion Rate ◽  
Filtration Rate ◽  
Urinary Output ◽  
Infusion Of Norepinephrine

The experiments of this study show that intravenous infusion of norepinephrine has a direct effect on the kidneys of areflex dogs to cause a decrease in renal blood flow, glomerular filtration rate, and urinary output. However, when the infusion rate is below an average of 0.0006 mg/kg/min, the renal blood flow, glomerular filtration rate, and urinary output increase as a result of an increase in arterial pressure which accompanies the infusion of norepinephrine. Above this infusion rate, the direct effect of the norepinephrine on the kidneys is greater than the effect of the rising arterial pressure, thus causing the blood flow, glomerular filtration rate, and urinary output to decrease. The results from this study indicate that changes in renal arterial pressure result in very significant changes in renal blood flow, glomerular filtration rate, and urinary output in spite of the local autoregulation of renal blood flow.

Transient response of glomerular filtration rate and renal blood flow to step changes in arterial pressure

1977 ◽  
Vol 233 (5) ◽  
pp. F396-F402 ◽  
Author(s):  
T. E. Jackson ◽  
A. C. Guyton ◽  
J. E. Hall
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Steady State ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Hemodynamic Changes ◽  
Proximal Tubular ◽  
Anesthetized Dogs

Measurement of rapid renal hemodynamic changes were made for 90 s in pentobarbital-anesthetized dogs following step increases and decreases in renal arterial pressure between 80 and 120 mm Hg. Transient analysis was used to observe time characteristics of the autoregulatory relationships which are obscured in steadystate measurements. Temporal decoupling of blood flow and glomerular filtration rate (GFR) occurred with both step increases and decreases of arterial pressure. Steady-state autoregulation of blood flow was attained in about 30 s, whereas steady-state autoregulation of GFR was not demonstrably attained even 90 s after the arterial pressure maneuver. The temporal decoupling of renal blood flow and GRR supports the concept of transient involvement of proximal tubular dynamics and efferent resistance changes during acute autoregulation of GFR following step changes in arterial pressure.

Effects of synthetic atrial natriuretic factor on renal function and renin release

1984 ◽  
Vol 247 (5) ◽  
pp. F863-F866 ◽  
Author(s):  
J. C. Burnett ◽  
J. P. Granger ◽  
T. J. Opgenorth
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Atrial Natriuretic Factor ◽  
Filtration Rate ◽  
Renin Secretion ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Studies were performed in anesthetized dogs (n = 5) to determine the effects of synthetic atrial natriuretic factor on renal function and renin release. Intrarenal infusion of synthetic atrial natriuretic factor (ANF) (0.3 microgram X kg-1 X min-1) resulted in a transient increase in renal blood flow (126 +/- 8 to 148 +/- 11 ml/min). The duration of this transient vasodilation was 3.1 +/- 0.4 min. Continued infusion was followed by a slight decrease in renal blood flow (126 +/- 8 to 117 +/- 8 ml/min) and an increase in glomerular filtration rate (23.1 +/- 3.5 to 30.7 +/- 1.9 ml/min), with filtration fraction thus being increased (0.19 +/- 0.04 to 0.27 +/- 0.03). These hemodynamic alterations were associated with increases in fractional sodium excretion (0.6 +/- 0.2 to 5.8 +/- 0.8%), fractional potassium excretion (30.8 +/- 9.4 to 56.3 +/- 7.4%), fractional lithium excretion (32.2 +/- 7.1 to 60.3 +/- 5.7%), and fractional phosphate excretion (8.7 +/- 3.5 to 41.6 +/- 11.7%). Intrarenal infusion of synthetic ANF markedly suppressed renin secretion rate (295.5 +/- 84.6 to 17.2 +/- 10.6 ng/min) despite a slight reduction in arterial pressure (123 +/- 9 to 118 +/- 9 mmHg). Our studies demonstrate that synthetic ANF results in a marked natriuretic response that is in part mediated by an increase in glomerular filtration rate. The increase in fractional lithium and phosphate excretion suggests that this factor may also have an action on proximal tubule reabsorption. Further, these studies demonstrate that synthetic ANF markedly inhibits renin secretion.

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)

Effect of a kinin antagonist on renal function and haemodynamics during alterations in sodium balance in conscious normotensive rats

1990 ◽  
Vol 78 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Paolo Madeddu ◽  
Nicola Glorioso ◽  
Aldo Soro ◽  
Paolo Manunta ◽  
Chiara Troffa ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Sodium Intake ◽  
Urinary Sodium Excretion

1. To evaluate whether sodium intake can modulate the action of endogenous kinins on renal function and haemodynamics, a receptor antagonist of bradykinin was infused in conscious normotensive rats maintained on either a normal or a low sodium diet. 2. The antagonist inhibited the hypotensive effect of exogenously administered bradykinin. It did not change the vasodepressor effect of acetylcholine, dopamine or prostaglandin E2. 3. The antagonist did not affect mean blood pressure, glomerular filtration rate, renal blood flow or urinary sodium excretion, in rats on sodium restriction. It did not change mean blood pressure, glomerular filtration rate or urinary sodium excretion, but decreased renal blood flow, in rats on a normal sodium intake. 4. The kallikrein–kinin system has a role in the regulation of renal blood flow in rats on a normal sodium diet.

scholarly journals RENAL FUNCTION DURING CHRONIC ANEMIA IN MAN

Blood ◽  
1947 ◽  
Vol 2 (2) ◽  
pp. 192-202 ◽  
Author(s):  
STANLEY E. BRADLEY ◽  
GERALDINE P. BRADLEY
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Normal Values ◽  
Renal Plasma Flow ◽  
Filtration Fraction ◽  
Chronic Anemia

Abstract 1. Renal function has been studied quantitatively in 15 patients with chronic anemia, 8 of whom were proved to have pernicious anemia. In 7 the anemia was secondary to chronic blood loss, iron deficiency, paroxysmal nocturnal hemoglobinuria, and leukemia. The effective renal plasma flow and glomerular filtration rate were measured by clearance technics; and tubular function, by saturation methods (diodrast Tm and glucose Tm). 2. The effective renal plasma flow, the glomerular filtration rate, and the filtration fraction (percentage of plasma filtered at the glomerulus) were reduced slightly below the normal values in most subjects. The effective renal whole blood flow was always greatly reduced, by 46 per cent on the average in males and by 31.8 per cent in females. 3. Since arterial pressure was not significantly depressed it was concluded that renal vasoconstriction occurs in chronic anemia, possibly as a homeostatic device for the diversion of blood to tissues more sensitive to oxygen lack. The relatively small reduction of filtration fraction implies afferent and efferent arteriolar vasoconstriction with dominance by the afferent arterioles. These changes were shown to be reversible, a return to normal values paralleling the return of the blood picture to normal. 4. Diodrast Tm was reduced significantly in 9 of 10 patients while the values of glucose Tm were normal in 6 of 7 patients. The normal values for glucose Tm indicated continued operation of all glomeruli and implied the absence of shunting or of cessation of blood flow in any significant portion of the kidney. The fall in diodrast Tm, which appeared to be reversible in 2 of 4 individuals, was interpreted as evidence of intracellular dysfunction rather than destruction or inactivation of nephrons.

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