POTASSIUM CHANNEL-MEDIATED RELAXATION TO ACETYLCHOLINE IN RABBIT ARTERIES

Endothelium-dependent relaxation is associated with smooth muscle hype rpolarization in many arteries which may account for relaxation that p ersists in the presence of nitric oxide inhibitors such as N(G)-nitro- L-arginine methyl ester (L-NAME). Acetylcholine (ACh)-induced relaxati ons of the rabbit thoracic and abdominal aorta and iliac and carotid a rteries were studied for the relative contribution of nitric oxide-dep endent and -independent mechanisms in rings suspended for measurement of isometric tension. Although relaxation of the thoracic aorta to ACh (10(-6) M) was almost blocked completely by L-NAME (3 x 10(-5) M), th e maximal relaxation in the abdominal aorta, carotid and iliac arterie s was only reduced by 28, 26 and 62%, respectively. In rings of abdomi nal aorta, L-NAME blocked the ACh-stimulated (10(-6) M) rise in cyclic GMP verifying that relaxation which persists in L-NAME-treated rings is not mediated by nitric oxide. The L-NAME resistant response was nea rly abolished by elevated external K+ in rings of abdominal aorta and carotid artery, suggesting this relaxation may be mediated by a membra ne potential sensitive mechanism. Furthermore, tetraethylammonium (10( -3) M) partially and charybdotoxin (5 x 10(-8 M) completely inhibited the remaining L-NAME-resistant relaxation in both abdominal aorta and carotid artery, suggesting a role for Ca++-activated K+-channels. Bloc kers of ATP-sensitive K+ channels also inhibited the L-NAME resistant relaxation in the abdominal aorta only. This study demonstrates hetero geneity in the responsiveness of different rabbit arteries to ACh and that this heterogeneity is due, at least in part, to the different con tribution of two distinct endothelium-dependent mechanisms; one which is nitric oxide-dependent and cyclic GMP-associated and the second whi ch depends on K+ channels.