Effect of Selective Inhibition of Soluble Guanylyl Cyclase on the K Ca Channel Activity in Coronary Artery Smooth Muscle

Abstract

Activation of a soluble guanylyl cyclase plays an important role in nitric oxide (NO)-induced vasodilation. Recently, we have reported that NO increases the calcium-activated potassium (K Ca ) channel activity in vascular smooth muscle cells from coronary arteries. The present study examined the role of the soluble guanylyl cyclase in the control of basal activity of the K Ca channels and in mediating NO-induced activation of the K Ca channels in vascular smooth muscle cells, using a selective inhibitor of this enzyme, 1 H -[1,2,4]oxadiazolo[4,2-α]quinoxalin-1-one (ODQ). In the cell-attached patch-clamp mode, addition of ODQ into the bath solution (10 μmol/L) decreased the K Ca channel activity by 59% and attenuated activation of the channels induced by the NO donor, deta nonoate, by 70%. ODQ had no effect on 8-bromo-cGMP-induced activation of the K Ca channels. Deta nonoate produced a concentration-dependent relaxation of precontracted coronary arteries. When ODQ was added to the bath, the deta nonoate-induced relaxations were inhibited. The IC 50 for deta nonoate was decreased by about 25-fold and the maximal effect of deta nonoate was reduced by about 60%. A specific K Ca channel inhibitor, iberiotoxin, decreased deta nonoate-induced vasodilation but to a lesser extent than ODQ. However, ODQ was without effect on the vasodilation induced by a prostacyclin analog, iloprost, and by adenosine. These results indicate that a soluble guanylyl cyclase and cGMP play an important role in the control of the K Ca channel activity in coronary arterial smooth muscle cells. K Ca channel activation participates in the NO-induced vasodilation in coronary circulation.