Effect of captopril on the vascular permeability changes induced by C5a, histamine and compound 48/80

Abstract

The modulating effect of captopril, an inhibitor of angiotensin-converting enzyme, on the vascular permeability changes induced by intradermal injections of C5a, histamine and compound 48/80, was evaluated in guinea pigs. Cutaneous vascular permeability changes were measured by the extravasation of i.v. injected 125I-bovine serum albumin. I.p. injection of 12.5, 25, or 50 mg/kg of captopril 30 min prior to the injection of C5a (10-11 mol) significantly enhanced the increase in vascular permeability induced by this agent (P < 0.02). This may be explained by the known property of captopril as an inhibitor of carboxypeptidase. No effect was observed when captopril was injected either 2 or 4 h before the injection of C5a. The same doses of captopril, when injected i.p. 2 h before the injection of histamine (10-8 mol) or compound 48/80 (10 .mu.g), significantly suppressed the increase in vascular permeability induced by these agents (P < 0.02). This suppressive effect occurred in a captopril dose-dependent manner. The ability of captopril to modulate the vascular permeability response induced by vasoactive agents indicates that it is a potentially useful tool to dissect the relative roles of mediators involved in inflammatory processes.