In vivo location and mechanism of EDHF-mediated vasodilation in canine coronary microcirculation

被引:90
作者
Nishikawa, Y [1 ]
Stepp, DW [1 ]
Chilian, WM [1 ]
机构
[1] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1999年 / 277卷 / 03期
关键词
coronary circulation; endothelium-dependent dilation; hyperpolarization; endothelium-derived hyperpolarizing factor;
D O I
10.1152/ajpheart.1999.277.3.H1252
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Responses of epicardial coronary arteriolos to ACh were measured using stroboscopic fluorescence microangiography in dogs (n = 38). ACh (0.1 and 0.5 pg mu g.kg(-1).min(-1) ic) dilated small (<100 mu m, 11 +/- 2 and 19 +/- 2%, respectively) and large (>100 mu m, 6 +/- 3 and 13 +/- 3%, respectively) arterioles at baseline. Combined administration of N-omega-monomethyl-L-arginine (L-NMMA; 1.0 mu mol/min icf and indomethacin (10 mg/kg iv) eliminated ACh-induced dilation in large coronary arterioles but only partially attenuated that in small arterioles. Suffusion of a buffer containing 60 mM KCI thigh KCI) completely abolished cromakalim-induced dilation in arterioles and in combination with L-NMMA plus indomethacin completely blocked ACh-induced dilation in small arterioles, This indicated that the vasodilation to ACh that persists in small arterioles after administration of L-NMMA and indomethacin is mediated via a hyperpolarizing factor. The ACh-induced vasodilation remaining after L-NMMA and indomethacin was completely blocked by the large-conductance potassium-channel antagonist iberiotoxin or by epicardial suffusion of miconazole or metyrapone, inhibitors of cytochrome P-450 enzymes. These observations are consistent with the view that endothelium-derived hyperpolarizing factor (EDHF) is a product of cytochrome P-450 enzymes and produces vasodilation by the opening of large-conductance potassium channels. We conclude that ACh-induced dilation in large coronary arterioles is mediated mainly by nitric oxide (NO), whereas, in small arterioles both NO and EDHF mediate dilation to ACh. These data provide the first direct evidence for an in vivo role of EDHF in small coronary arterioles.
引用
收藏
页码:H1252 / H1259
页数:8
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