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

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 intravenously injected 125I-bovine serum albumin. Intraperitoneal 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 less than 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. In contrast, the same doses of captopril, when injected intraperitoneally 2 h before the injection of histamine (10(-8) mol) or compound 48/80 (10 micrograms), significantly suppressed the increase in vascular permeability induced by these agents (P less than 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.