Femtomolar bradykinin‐induced relaxation of isolated bovine coronary arteries, mediated by endothelium‐derived nitric oxide

We reported previously that bradykinin induces endothelium‐dependent relaxation at nanomolar (n M ) concentrations in isolated bovine coronary arteries with an intact endothelium. Recently we have found that in the presence of 10 μ m indomethacin, femtomolar (f M ) concentrations of bradykinin induce endothelium‐dependent relaxation in some bovine coronary arteries (≈ 10% of the coronary arteries examined). The present study was designed to characterize the relaxation induced by f M bradykinin. Relaxation was completely abolished by repeated application of f M bradykinin, by 100 μ m N ω ‐ nitro‐ l ‐ arginine methyl ester and by 10 μ m methylene blue. Relaxation induced by n M bradykinin was partly affected by these treatments. Relaxation induced by both concentrations of bradykinin was inhibited by a B 2 ‐kinin receptor antagonist, [Thi 5,8 , D‐Phe 7 ]‐bradykinin, in a concentration‐dependent manner, but not by a B 1 ‐kinin receptor antagonist, des‐Arg 9 , [Leu 8 ]‐bradykinin. In the presence of 10 μ m captopril, an angiotensin‐converting enzyme (ACE) inhibitor, all coronary arteries examined in this experiment showed endothelium‐dependent relaxation to f M bradykinin. These results show that some bovine coronary arteries relax in response to f M 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.