This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, P.-L. Articles by Campbell, W. B. Search for Related Content PubMed PubMed Citation Articles by Li, P.-L. Articles by Campbell, W. B.

(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

This article has been cited by other articles:

				J. Han, N. Kim, H. Joo, and E. Kim Ketamine blocks Ca2+-activated K+ channels in rabbit cerebral arterial smooth muscle cells Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1347 - H1355. [Abstract] [Full Text] [PDF]

				T. Komuro, M. K. Borsody, S. Ono, L. S. Marton, B. K. Weir, Z.-D. Zhang, E. Paik, and R. L. Macdonald The Vasorelaxation of Cerebral Arteries by Carbon Monoxide Experimental Biology and Medicine, October 1, 2001; 226(9): 860 - 865. [Abstract] [Full Text] [PDF]

				A. Revelli, C. Costamagna, F. Moffa, E. Aldieri, S. Ochetti, A. Bosia, M. Massobrio, B. Lindblom, and D. Ghigo Signaling Pathway of Nitric Oxide-Induced Acrosome Reaction in Human Spermatozoa Biol Reprod, June 1, 2001; 64(6): 1708 - 1712. [Abstract] [Full Text]

				J.-Z. Yu, D. X. Zhang, A.-P. Zou, W. B. Campbell, and P.-L. Li Nitric oxide inhibits Ca2+ mobilization through cADP-ribose signaling in coronary arterial smooth muscle cells Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H873 - H881. [Abstract] [Full Text] [PDF]

				C.-W. Sun, J. R. Falck, H. Okamoto, D. R. Harder, and R. J. Roman Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H339 - H350. [Abstract] [Full Text] [PDF]

				J. Geiger, A.-P. Zou, W. B. Campbell, and P.-L. Li Inhibition of cADP-Ribose Formation Produces Vasodilation in Bovine Coronary Arteries Hypertension, January 1, 2000; 35(1): 397 - 402. [Abstract] [Full Text] [PDF]

				D. Li, N. Zhou, and R. A. Johns Soluble guanylate cyclase gene expression and localization in rat lung after exposure to hypoxia Am J Physiol Lung Cell Mol Physiol, October 1, 1999; 277(4): L841 - L847. [Abstract] [Full Text] [PDF]

				R. D. Swayze and A. P. Braun A Catalytically Inactive Mutant of Type I cGMP-dependent Protein Kinase Prevents Enhancement of Large Conductance, Calcium-sensitive K+ Channels by Sodium Nitroprusside and cGMP J. Biol. Chem., June 1, 2001; 276(23): 19729 - 19737. [Abstract] [Full Text] [PDF]

				M. Yu, C.-W. Sun, K. G. Maier, D. R. Harder, and R. J. Roman Mechanism of cGMP contribution to the vasodilator response to NO in rat middle cerebral arteries Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1724 - H1731. [Abstract] [Full Text] [PDF]