Comparison of the effect of imidaprilat and ramiprilat on bronchoconstriction and hypotension induced by bradykinin in guinea pigs

Abstract:

Objective: To demonstrate tissue selective bradykinin (BK) potentiating action of angiotensin converting enzyme inhibitors, we studied effects of imidaprilat and ramiprilat, active metabolites of imidapril and ramipril, respectively, on bronchoconstriction and hypotension both induced by BK in vasopressin-infused anesthetized guinea pigs.¶Methods: We measured pulmonary inflation pressure and blood pressure in vasopressin-infused anesthetized guinea pigs at the same time. BK-induced changes in pulmonary inflation pressure and blood pressure before and after the administration of ACE inhibitor were compared.¶Results: Imidaprilat and ramiprilat enhanced BK-induced hypotension comparably, and this effect was inhibited by N ^{$ \omega $}-nitro-L-arginin-methylester (L-NAME, a nitric oxide synthetase inhibitor). Although imidaprilat did not affect BK-induced bronchoconstriction, ramiprilat enhanced the bronchoconstriction significantly. SR48968, a selective NK₂ receptor antagonist, significantly inhibited the enhancing effect of ramiprilat on BK-induced bronchoconstriction.¶Conclusion: These results suggest that enhancement of BK-induced hypotension by imidaprilat and ramiprilat is mediated by nitric oxide (NO), but the mediator of the enhancing action of ramiprilat on BK-induced bronchoconstriction is mainly neurokinin A.¶