ENHANCED ROLE OF K-ARTERY TO NO( CHANNELS IN RELAXATIONS OF HYPERCHOLESTEROLEMIC RABBIT CAROTID)

Endothelium-dependent relaxations to acetylcholine remain normal in th e carotid artery of hypercholesterolemic rabbits, but unlike endotheli um-dependent relaxations of normal rabbits, they are inhibited by char ybdotoxin, a specific blocker of Ca2+-dependent K+ channels. Because n itric oxide (NO) is the mediator of endothelium-dependent relaxation a nd can activate Ca2+-dependent K+ channels directly or via guanosine 3 ',5'-cyclic monophosphate, the present study investigated the role of Ca2+-dependent K+ channels in relaxations caused by NO, sodium nitropr usside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was meas ured in rabbit carotid artery denuded of endothelium from normal and h ypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in n ormal and hypercholesterolemic rabbit arteries. Charybdotoxin had no s ignificant effect on relaxations of normal arteries to NO, sodium nitr oprusside, or 8-BrcGMP, but the Ca2+-dependent K+ channel blocker sign ificantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxatio ns to the calcium channel blocker nifedipine were potentiated to a sim ilar extent by charybdotoxin in both groups. In addition, arteries fro m hypercholesterolemic rabbits relaxed less than normal to sodium nitr oprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca2+-dependent K+ channels. T hese data also suggest that K+ channel-independent mechanism(s) are im paired in hypercholesterolemia.