Effects of the renal vasodilator prodrug CGP 22 979A and its parent compound CGP 18 137A on renal and central hemodynamics in conscious spontaneously hypertensive rats

HM Nievelstein, H van Essen, R Hornsveld, HA Struyker-Boudier and JF Smits

In a previous study we reported that the renal prodrug CGP 22 979A (N- acetyl-L-glutamic acid-N-[N2-(5-n-butyl-2-pyridyl)-hydrazide) causes selective renal vasodilation in conscious spontaneously hypertensive rats (SHR) in doses up to 10 mg/kg. The hydralazine-like parent compound CGP 18 137A (2-hydrazino-5-n-butyl-pyridine) causes general vasodilatation. In the present study we report on renal hemodynamics, excretion of water and sodium and central hemodynamic effects of CGP 18 137A and CGP 22 979A in conscious, unrestrained SHR. CGP 18 137A (1 mg/kg) reduced effective renal plasma flow [measured as plasma clearance of [125I]p-aminohippuric acid] and glomerular filtration rate (measured as plasma-clearance of 51Cr-EDTA), in the first hour after injection. CGP 22 979A (3-30 mg/kg) dose-dependently increased effective renal plasma flow, but not glomerular filtration rate thus reducing filtration fraction. In spite of the lack of increase of glomerular filtration rate, CGP 22 979A increased excretion of sodium and water in a separate group of SHR. CGP 18 137A reduced renal excretory function slightly. In another group of conscious SHR we studied the effects of CGP 18 137A and CGP 22 979A on central hemodynamics. These animals had an electromagnetic flow-probe on the ascending aorta, to measure cardiac output (CO). Mean arterial pressure was measured from a chronic catheter in the abdominal aorta. Total peripheral resistance (TPR) and stroke volume were calculated. CGP 18 137A (0.3-1 mg/kg) reduced mean arterial pressure and TPR whereas CO increased immediately after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 235, Issue 3, pp. 778-782, 12/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics