Nitric Oxide Accounts for Endothelium‐dependent Relaxation of Pig Coronary Artery in Response to Noradrenaline

Vasorelaxant substances responsible for endothelium-dependent relaxation of pig coronary artery in response to noradrenaline have been investigated pharmacologically. Noradrenaline relaxed pig coronary artery in an endothelium- and concentration-dependent way in the presence of prazosin (10−6 M) and propranolol (3 times 10−6 M), to block α1- and β-adrenoceptors in smooth muscle cells. Prazosin- and propranolol-resistant endothelium-dependent relaxation of the coronary artery to noradrenaline was greatly attenuated by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (10−4 M) and the soluble guanylate cyclase inhibitor (1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, ODQ; 10−5 M). Noradrenaline-induced endothelium-dependent coronary relaxation in the presence of prazosin and propranolol was almost abolished by rauwolscine (3 times 10−6 M), a selective α2-adrenoceptor antagonist. These findings suggest that noradrenaline-induced endothelium-dependent relaxation of pig coronary artery is largely mediated by release of endothelium-derived NO as a consequence of the stimulation of endothelial α2-adrenoceptors.