Key result
Captopril significantly decreased mean arterial blood pressure and renal vascular resistance while increasing urine flow and GFR in dehydrated sheep, effects that were blocked by sarileucin.
Why the study?
Does captopril alter renal function and blood pressure in dehydrated sheep, and are these effects mediated by angiotensin II?
Does captopril alter renal function and blood pressure in dehydrated sheep, and are these effects mediated by angiotensin II?
Captopril's effects on renal function and blood pressure in dehydrated sheep are mediated by decreased angiotensin II levels rather than bradykinin potentiation.
Cautions against clinical extrapolation in dehydrated patients; hypothesis-generating for angiotensin II mediation of ACE inhibitor effects in animal models.
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 (Cosm), solute-free water reabsorption (TC, 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, 1-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., Cosm and TC, H2O. This apparent mixture of AII agonist and antagonist properties probably accounts for the absence of any change in M.A.B.P. or P.R.A. during sarileucin administration.
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Yesberg et al. (1984) studied Dehydrated (n=9). Captopril vs. Pretreatment with sarileucin was evaluated on Renal function parameters (M.A.B.P., R.V.R., urine flow, sodium excretion, G.F.R., etc.). Captopril significantly decreased mean arterial blood pressure and renal vascular resistance while increasing urine flow and GFR in dehydrated sheep, effects that were blocked by sarileucin.
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