Effects of KB-2796, a New Diphenylpiperazine Calcium Antagonist, on Renal Hemodynamics and Urine Formation in Anesthetized Dogs

Abstract

ABSTRACT-The effects of KB-2796, a new calcium antagonist with a diphenylpiperazine moiety, on renal hemodynamics and urine formation were investigated in anesthetized dogs. Intravenous infusion of KB-2796 (10, 30, and 100,ug/kg/min) decreased mean blood pressure (MBP) and renal vascular re sistance (RVR) in a dose-dependent manner, but did not change renal blood flow (RBF). At the high est dose, glomerular filtration rate (GFR) and urine flow (UF) -tended to decrease. Nicardipine (0.1, 0.3, and lug/kg/min) also dose-dependently decreased MBP, RVR, GFR, and UF. When KB-2796 was infused into the renal artery at lower doses of 3 and 10,ug/kg/min, OF and urinary excretion of electrolytes increased without a significant change in RBF and GFR. Intrarenal infusion of KB-2796 at 30,ug/kg/min and nicardipine at 0.3,ug/kg/min produced a significant increase in GFR, RBF, UF, urinary excretion of electrolytes, and renin secretion rate. These results suggest that KB-2796 adminis tered intrarenally exerts a diuretic action via tubular effects and the alteration of renal hemodynamics. However, its diuretic action might be masked by diminished urine formation via a reflex activation of the sympathetic nerves and/or via a reduction of renal perfusion pressure when it is administered sys temically.

A Comparison of the Uricosuric Effects in Rats of Diltiazem and Derivatives of Dihydropyridine (Nicardipine and Nifedipine).

“…Our results are in agreement with those in our own and other reports: diltiazem (9) and nifedipine (15) increased RBF in rats after i.v. infusion, and intrarenal infusion of nicardipine increased RBF in dogs (12)(13)(14). Surgical correction of renal hemodynamics, namely, sim ple correction of reduced RBF leads to reduction in the serum concentration of uric acid (16).…”