ENHANCED ROLE OF POTASSIUM CHANNELS IN RELAXATIONS TO ACETYLCHOLINE IN HYPERCHOLESTEROLEMIC RABBIT CAROTID-ARTERY

The effect of hypercholesterolemia for 10 wk on endothelium-dependent relaxations to acetylcholine was studied in isolated rings of rabbit c arotid artery and abdominal aorta contracted with phenylephrine or ele vated potassium. In these arteries obtained from hypercholesterolemic rabbits, endothelium-dependent relaxations to acetylcholine were not s ignificantly different from those of normal rabbits. In normal and hyp ercholesterolemic arteries, partial relaxation persisted in the presen ce of N-G-nitro-L-arginine methyl ester (L-NAME), which blocked acetyl choline-induced increases in arterial guanosine 3',5'-cyclic monophosp hate (cGMP). Combined treatment with L-NAME and the calcium-dependent potassium-channel inhibitor, charybdotoxin, blocked relaxations in bot h groups, suggesting that L-NAME-resistant relaxations are mediated by an endothelium-derived hyperpolarizing factor. Charybdotoxin alone or depolarizing potassium had no significant effect on normal carotid ar tery or normal and hypercholesterolemic abdominal aorta but significan tly inhibited relaxations of the carotid artery from cholesterol-fed r abbits. The enhanced role of calcium-dependent potassium channels and the hyperpolarizing factor in relaxation of the hypercholesterolemic c arotid artery suggested by these results was likely related to the fac t that acetylcholine failed to stimulate cGMP only in that artery. The se data suggest that endothelium-dependent relaxation in these rabbit arteries is mediated by nitric oxide-cGMP-dependent and -independent m echanisms. In hypercholesterolemia, the contribution of nitric oxide-c GMP in the carotid artery is reduced, but a hyperpolarizing factor and calcium-dependent potassium channels maintain normal acetylcholine-in duced relaxation.