EFFECT OF SELECTIVE-INHIBITION OF SOLUBLE GUANYLYL CYCLASE ON THE K-CA CHANNEL ACTIVITY IN CORONARY-ARTERY SMOOTH-MUSCLE

Activation of a soluble guanylyl cyclase plays an important role in ni tric oxide (NO)-induced vasodilation. Recently, we have reported that NO increases the calcium-activated potassium (K-Ca) channel activity i n vascular smooth muscle cells from coronary arteries. The present stu dy examined the role of the soluble guanylyl cyclase in the control of basal activity of the K-Ca channels and in mediating NO-induced activ ation of the K-Ca channels in vascular smooth muscle cells, using a se lective inhibitor of this enzyme, 1H-[1,2,4]oxadiazolo[4,2-alpha]quino xalin-1-one (ODQ). In the cell-attached patch-clamp mode, addition of ODQ into the bath solution (10 mu mol/L) decreased the K-Ca channel ac tivity 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-ind uced activation of the K-Ca channels. Deta nonoate produced a concentr ation-dependent relaxation of precontracted coronary arteries. When OD Q was added to the bath, the deta nonoate-induced relaxations were inh ibited. The IC50 for deta nonoate was decreased by about 25-fold and t he maximal effect of deta nonoate was reduced by about 60%. A specific K-Ca channel inhibitor, iberiotoxin, decreased deta nonoate-induced v asodilation 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 cycl ase and cGMP play an important role in the control of the K-Ca channel activity in coronary arterial smooth muscle cells. K-Ca channel activ ation participates in the NO-induced vasodilation in coronary circulat ion.