Inhibitory effect of nisoldipine on angiotensin-II-induced renal actions in anesthetized dogs.
Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anesthetized dogs. Intrarenal arterial infusion of nisoldipine (2, 10, and 50 ng/kg per min) had no effect on mean systemic blood pressure and heart rate and there was no significant change in renal hemodynamics during infusion of various doses of the drug. Urine flow and urinary excretions of sodium, chloride, and potassium were increased by nisoldipine in a dose-related manner. Fractional excretions of sodium and chloride were markedly elevated with the highest dose given thereby indicating that tubular reabsorptions of sodium and chloride were inhibited by nisoldipine. Nisoldipine (50 ng/kg per min) abolished the decreasing effects of angiotensin-II on glomerular filtration rate, urine flow, and urinary excretion of electrolytes but not the decrease in renal blood flow by the peptide. Angiotensin-II-induced reduction of fractional excretion of electrolytes was completely blocked by nisoldipine. Renal responses to norepinephrine were unaffected by nisoldipine. Thus, nisoldipine administered intrarenally to anesthetized dogs exerts a diuretic action by way of tubular effects, as is the case with other dihydropyridine calcium channel blockers. Nisoldipine seems to effectively antagonize the renal response to angiotensin-II. Thus, the preferential inhibition of angiotensin-II-induced antidiuresis may mean that nisoldipine interferes with stimulatory effects of angiotensin-II on the renal tubular reabsorption of electrolytes and water.
Kageyama
M
M
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Sasaki
Y
Y
Ichihara
T
T
Hosokawa
T
T
Hayashi
K
K
Morimoto
S
S
D000758:Anesthesia; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D004285:Dogs; D005260:Female; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D009638:Norepinephrine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects
D000804:Angiotensin II; D015737:Nisoldipine; D009543:Nifedipine; D009638:Norepinephrine