Li P L, Jin M W, Campbell W B
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
Hypertension. 1998 Jan;31(1 Pt 2):303-8. doi: 10.1161/01.hyp.31.1.303.
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-alpha]quinoxalin-1-one (ODQ). In the cell-attached patch-clamp mode, addition of ODQ into the bath solution (10 micromol/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.
可溶性鸟苷酸环化酶的激活在一氧化氮（NO）诱导的血管舒张中起重要作用。最近，我们报道NO可增加冠状动脉血管平滑肌细胞中钙激活钾（K（Ca））通道的活性。本研究使用该酶的选择性抑制剂1H-[1,2,4]恶二唑并[4,2-α]喹喔啉-1-酮（ODQ），研究了可溶性鸟苷酸环化酶在控制K（Ca）通道基础活性以及介导NO诱导的血管平滑肌细胞中K（Ca）通道激活方面的作用。在细胞贴附式膜片钳模式下，向浴液中加入ODQ（10 μmol/L）可使K（Ca）通道活性降低59%，并使NO供体二乙三胺 NONO 酸盐诱导的通道激活减弱70%。ODQ对8-溴-cGMP诱导的K（Ca）通道激活无影响。二乙三胺 NONO 酸盐可使预收缩的冠状动脉产生浓度依赖性舒张。当向浴液中加入ODQ时，二乙三胺 NONO 酸盐诱导的舒张受到抑制。二乙三胺 NONO 酸盐的半数抑制浓度（IC50）降低约25倍，其二乙三胺 NONO 酸盐的最大效应降低约60%。一种特异性K（Ca）通道抑制剂iberiotoxin可降低二乙三胺 NONO 酸盐诱导的血管舒张，但程度小于ODQ。然而，ODQ对前列环素类似物伊洛前列素和腺苷诱导的血管舒张无影响。这些结果表明，可溶性鸟苷酸环化酶和cGMP在冠状动脉平滑肌细胞K（Ca）通道活性的控制中起重要作用。K（Ca）通道激活参与冠状动脉循环中NO诱导的血管舒张。
