CONVERTING-ENZYME INHIBITION AND 1-SARCOSINE-8-ISOLEUCINE-ANGIOTENSIN II: EFFECTS ON RENAL FUNCTION IN THE DEHYDRATED SHEEP

¹ Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia 4067

The effect of a converting-enzyme inhibitor (captopril) was studied in nine conscious dehydrated Merino ewes. Captopril (4 mg I.V. over 40 min) caused significant decreases in mean arterial blood pressure (M.A.B.P.), renal vascular resistance (R.V.R.) and filtration fraction, and increases in urine flow (V), sodium excretion, glomerular filtration rate (G.F.R.), renal plasma flow, solute clearance (C_osm), solute-free water reabsorption (T_C,H2O) and plasma renin activity (P.R.A.). None of these effects was observed when captopril was similarly administered to sheep pretreated with angiotensin II (AII) receptor blocker, l-sarcosine-8-isoleucine-AII (sarileucin). It is concluded that the effects of captopril were probably not due to bradykinin potentiation but rather to decreased levels of circulating AII. The effect of sarileucin itself was complex. It effectively blocked the pressor response to administered AII, but it also had an AII-like effect indicated by a rise in R.V.R., and decreases in V, G.F.R., C_osm and T_C,H2O. This apparent mixture of All agonist and antagonist properties probably accounts for the absence of any change in M.A.B.P. or P.R.A. during sarileucin administration.