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(Hypertension. 1998;31:303.)
© 1998 American Heart Association, Inc.

Scientific Contributions

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

Pin-Lan Li; Man-Wen Jin; William B. Campbell

From the Departments of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis.

Correspondence to Pin-Lan Li, MD, PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. pli{at}post.its.mcw.edu

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, 1H-[1,2,4]oxadiazolo[4,2-]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 IC₅₀ 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.

Key Words: potassium channels • nitric oxide • endothelium • guanylyl cyclase • vasodilation • coronary artery

Abbreviations: K_Ca = calcium-activated potassium • NO = nitric oxide • NOS = nitric oxide synthase • ODQ = 1H-1,2,4-oxadiazolo[4,2-]quinoxalin-1-one • PKG = protein kinase G • VSM = vascular smooth muscle

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