INVOLVEMENT OF MAXI-K-CA CHANNEL ACTIVATION IN ATRIAL NATRIURETIC PEPTIDE-INDUCED VASORELAXATION

Large conductance, voltage- and Ca2+-sensitive K+ (maxi-K-Ca) channels play an important role in the regulation of vascular smooth muscle ex citability and contractility. The activity of maxi-K-Ca channels is mo dified by a variety of intracellular messengers including cGMP, as wel l as by voltage and Ca2+. In the present study, we investigated the fu nctional relevance of maxi-Kc, channels in atrial natriuretic peptide (ANP)-mediated vasorelaxation in the isolated rat mesenteric artery. A NP produced concentration-dependent relaxation in the de-endothelializ ed rat mesenteric artery. Iberiotoxin, a specific blocker of maxi-K-Ca channels, greatly attenuated the ANP-induced vasorelaxation. Similarl y, a large portion of the vascular relaxation induced by 8-Bromo-cGMP, a membrane permeable analogue of cGMP, was inhibited by iberiotoxin. These results indicate that activation of maxi-K-Ca channels contribut es substantially to the vascular relaxation produced by ANP in the rat mesenteric artery. Intracellular cGMP, increased by ANP, and the subs equent activation of cGMP-dependent protein kinase (PKG) may play a ce ntral role in the activation of maxi-K-Ca channels in the ANP-produced vascular relaxation.