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 excitability and contractility. The activity of maxi-K(Ca) channels is modified by a variety of intracellular messengers including cGMP, as well as by voltage and Ca2+. In the present study, we investigated the functional relevance of maxi-K(Ca) channels in atrial natriuretic peptide (ANP)-mediated vasorelaxation in the isolated rat mesenteric artery. ANP produced concentration-dependent relaxation in the de-endothelialized rat mesenteric artery. Iberiotoxin, a specific blocker of maxi-K(Ca) channels, greatly attenuated the ANP-induced vasorelaxation. Similarly, 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 contributes substantially to the vascular relaxation produced by ANP in the rat mesenteric artery. Intracellular cGMP, increased by ANP, and the subsequent activation of cGMP-dependent protein kinase (PKG) may play a central role in the activation of maxi-K(Ca) channels in the ANP-produced vascular relaxation.