DIFFERENCE AMONG ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN POTENTIATING EFFECTS ON BRADYKININ-INDUCED MICROVASCULAR LEAKAGE IN GUINEA-PIGAIRWAYS

We investigated the effect of imidapril, a novel angiotensin-convertin g enzyme (ACE) inhibitor, on augmentation of airway microvascular leak age induced by bradykinin (BK) and substance P (SP) in guinea pigs and compared it with those of enalapril and captopril. The three ACE inhi bitors significantly potentiated BK- and SP-induced airway microvascul ar leakage in a dose-dependent manner. In spite of the compatible or h igher ACE inhibitory activity of imidapril, its potentiating activity in BK-induced leakage was lower than those of enalapril and captopril both by single administration (0.3-30 mg/kg, p.o.) and repeated admini stration for eight days (0.1-10 mg/kg/day, p.o.). The potentiating act ivities of the three ACE inhibitors were suppressed by pretreatment wi th a BK2-receptor antagonist, but not by neurokinin 1 and neurokinin 2 antagonists, suggesting that neurokinins may not be involved in BK-in duced leakage under, the conditions used. On the other hand, the poten tiating effect of imidapril in SP-induced leakage was weaker than thos e of enalapril and captopril only after single high doses. The present study shows that the ACE inhibitors have different activity in potent iation of the airway microvascular leakage induced by BK, which may be ascribable to the difference in their inhibition of BK hydrolysis. Th is evidence may partly explain the smaller incidence of dry cough indu ced by imidapril compared with other ACE inhibitors when clinically us ed as antihypertensive drugs.