Effects of KB-2796, a new diphenylpiperazine calcium antagonist, on renal hemodynamics and urine formation in anesthetized dogs.
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 micrograms/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 microgram/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 micrograms/kg/min, UF and urinary excretion of electrolytes increased without a significant change in RBF and GFR. Intrarenal infusion of KB-2796 at 30 micrograms/kg/min and nicardipine at 0.3 microgram/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.
Iwamoto
T
T
Department of Pharmacology, New Drug Research Laboratories, Kanebo Ltd., Osaka, Japan.
Morita
T
T
Sukamoto
T
T
Ito
K
K
D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood / Q000378:metabolism
D002121:Calcium Channel Blockers; D010879:Piperazines; D009529:Nicardipine; C052424:lomerizine; D012083:Renin