Inhibitory effects of nisoldipine and saralasin on angiotensin II-induced antidiuresis in anesthetized dogs.
Inhibitory effects of the calcium channel blocker nisoldipine on angiotensin II-induced antidiuresis were investigated in anesthetized dogs, and the findings were compared with those of saralasin. Intrarenal arterial infusion of 10 ng/kg/min angiotensin II resulted in marked decreases in renal blood flow (RBF) and urine formation, with a relatively moderate decrease in glomerular filtration rate. There were marked reductions in the fractional excretion of lithium, which is used as an index of the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. Nisoldipine (50 ng/kg/min) administered intrarenally produced a partial inhibition on the decreased response of RBF to angiotensin II. The peptide-induced decreases in urine flow, urinary excretion of electrolytes and fractional excretion of electrolytes were abolished by nisoldipine. In contrast, when saralasin was administered intrarenally at 10 ng/kg/min, a dose which could partially inhibit the angiotensin II-induced decrease in RBF to the same extent as seen with nisoldipine, the antagonist attenuated, but did not abolish, the antidiuretic action of angiotensin II. Significant decreases in urine formation by angiotensin II were observed, even in the presence of saralasin. These results suggest that nisoldipine, unlike saralasin, preferentially interferes with the stimulatory effect of angiotensin II, as related to the renal tubular reabsorption of sodium and water.
Kageyama
M
M
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Hayashi
K
K
Hosokawa
T
T
Morimoto
S
S
D000758:Anesthesia; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D004573:Electrolytes / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008094:Lithium / Q000378:metabolism; D015737:Nisoldipine / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology*
D004573:Electrolytes; D000804:Angiotensin II; D015737:Nisoldipine; D008094:Lithium; D012504:Saralasin