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

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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 μg/kg/min) decreased mean blood pressure (MBP) and renal vascular resistance (RVR) in a dose-dependent manner, but did not change renal blood flow (RBF). At the highest dose, glomerular filtration rate (GFR) and urine flow (UF) -tended to decrease. Nicardipine (0.1, 0.3, and 1 μg/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 μg/kg/min, UF and urinary excretion of electrolytes increased without a significant change in RBF and GFR. Intrarenal infusion of KB-2796 at 30 μg/kg/min and nicardipine at 0.3 μg/kg/min produced a significant increase in GFR, RBF, UF, urinary excretion of electrolytes, and renin secretion rate. These results suggest that KB-2796 administered 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 systemically.
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