FEMTOMOLAR BRADYKININ-INDUCED RELAXATION OF ISOLATED BOVINE CORONARY-ARTERIES, MEDIATED BY ENDOTHELIUM-DERIVED NITRIC-OXIDE

We reported previously that bradykinin induces endothelium-dependent r elaxation at nanomolar (nM) concentrations in isolated bovine coronary arteries with an intact endothelium. Recently we have found that in t he presence of 10 mu M indomethacin, femtomolar (fM) concentrations of bradykinin induce endothelium-dependent relaxation in some bovine cor onary arteries (approximate to 10% of the coronary arteries examined). The present study was designed to characterize the relaxation induced by fM bradykinin. Relaxation was completely abolished by repeated app lication of fM bradykinin, by 100 mu M N-omega-nitro-L-arginine methyl ester and by 10 mu M methylene blue. Relaxation induced by nM bradyki nin was partly affected by these treatments. Relaxation induced by bot h concentrations of bradykinin was inhibited by a B-2-kinin receptor a ntagonist, [Thi(5,8), D-Phe(7)]-bradykinin, in a concentration-depende nt manner, but not by a B-1-kinin receptor antagonist, des-Arg(9), [Le u(8)]-bradykinin. In the presence of 10 mu M captopril, an angiotensin -converting enzyme (ACE) inhibitor, all coronary arteries examined in this experiment showed endothelium-dependent relaxation to fM bradykin in, These results show that some bovine coronary arteries relax in res ponse to fM bradykinin, and this response is mediated predominantly by the release of nitric oxide via stimulation of endothelial B-2-kinin receptors. The relaxation may be dependent on ACE activity.