Mechanism of the Protective Effect of Angiotensin-Converting Enzyme Inhibition in Hemorrhagic Shock

Anesthetized cats subjected to hemorrhage were treated with captopril, a CEI (0.5 μg/kg/hr) alone or in conjunction with angiotensin II (10 μg/kg/hr). Angioten-sin II administration significantly reduced survival time (110 vs 64 min) and lowered superior mesenteric artery flow (SMAF) immediately after reinfusion (8.5 vs 2.2 ml/kg/ min). These results suggest that blockade of angiotensin II formation is a prominent aspect of the beneficial actions of captopril in hemorrhage. Furthermore, captopril potentiated the vascular effects of bradykinin at normal blood pressures but not in hemor-rhagic hypotension. In the same experiments, captopril blocked the vascular effects of angiotensin I at both pressures. Thus, bradykinin potentiation is not essential for the beneficial actions of captopril in hemorrhagic shock, since hypotension abolishes the bra-dykinin-potentiating effects of captopril. Reduction of angiotensin II formation appears to be a major mechanism of captopril action in prolonging survival after hemorrhage.