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 (nM) concentrations in isolated bovine coronary arteries with an intact endothelium. Recently we have found that in the presence of 10 microM indomethacin, femtomolar (fM) concentrations of bradykinin induce endothelium-dependent relaxation in some bovine coronary arteries (approximately 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 application of fM bradykinin, by 100 microM N(omega)-nitro-L-arginine methyl ester and by 10 microM methylene blue. Relaxation induced by nM bradykinin was partly affected by these treatments. Relaxation induced by both concentrations of bradykinin was inhibited by a B2-kinin receptor antagonist, [Thi5,8, D-Phe7]-bradykinin, in a concentration-dependent manner, but not by a B1-kinin receptor antagonist, des-Arg9, [Leu8]-bradykinin. In the presence of 10 microM captopril, an angiotensin-converting enzyme (ACE) inhibitor, all coronary arteries examined in this experiment showed endothelium-dependent relaxation to fM bradykinin. These results show that some bovine coronary arteries relax in response to fM bradykinin, and this response is mediated predominantly by the release of nitric oxide via stimulation of endothelial B2-kinin receptors. The relaxation may be dependent on ACE activity.
Nakamura
Y
Y
Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Korimoto, Japan.
Kawagoe
K
K
Obi
T
T
Miyamoto
A
A
Ishiguro
S
S
Nishio
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; D002216:Captopril; D001920:Bradykinin; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester