Human coronary arteriolar dilation to bradykinin depends on membrane hyperpolarization -: Contribution of nitric oxide and Ca2+-activated K+ channels
Human coronary arteriolar dilation to bradykinin depends on membrane hyperpolarization -: Contribution of nitric oxide and Ca2+-activated K+ channels
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DOI：
10.1161/01.cir.99.24.3132
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发表时间：
1999-06-22
期刊：
影响因子：
37.8
通讯作者：
Gutterman, DD
中科院分区：
文献类型：
--
作者：
Miura, H;Liu, YP;Gutterman, DD
血管平滑肌细胞（VSMCs）中的k +通道激活在调节血管张力中起关键作用。内皮衍生的超极化因子（EDHF）比一氧化氮（NO）更有助于微血管扩张。超极化对人类冠状动脉扩张是否重要尚不清楚。缓激肽（brykinin， BK）是一种内源性血管活性物质，可从缺血心肌中释放，调节冠状动脉阻力，因此，我们在离体人冠状动脉微血管中测试了抑制NO合酶、环氧化酶和K+通道对BK响应的直径和膜电位（Em）变化的影响。方法与结果：取78例右心房附件小动脉（97 +/- 4 μ m: n = 120），在60mmhg的扩张压力和零流量下插管。同时测量血管直径（视频显微镜）和VSMC Em（玻璃微电极）的变化。在血管收缩和去极化（Em； -50 +/- 3至-28 +/- 2 mV）与内皮素-1 （ET）。与硝普钠（SNP）的扩张（-34 +/- 2 mV, 10(-4) mol/L）相比，对BK的扩张在10(-6)mol/L时具有更大的膜超极化（-48 +/- 3 mV）。n - ω -硝基-L-精氨酸甲酯（L- name; 10(-4) mol/L），一种NO合成酶抑制剂，部分降低了对BK的扩张（最大扩张61 +/- 10%，对照组92 +/- 4%:P < 0.05）， Charybdotoxin （CTX; 10(-8) mol/L）。一个large-conductance Ca2 +激活K +通道阻滞剂,ol apamin (10 (7) mol / L),一个small-conductance Ca2 +激活K +通道阻断剂,抑制膨胀(CTX 22 + / - 6%, apamin 45 + / - 10%控制69 + / - 6%;P < 0.05)和膜超极化(CTX -31 + / - 2 mV apamin -37 + / - 2 mV和控制-44 + / - 2 mV; P < 0.05) BK,而格列本脲(10 (6)mol / L),一个ATP-sensitive K +通道阻滞剂,没有效果。结论：人冠状动脉对BK的血管扩张在很大程度上依赖于Ca2+激活的K+通道激活的膜超极化，内皮源性NO的作用明显较小。这表明K+通道激活在调节人冠状动脉tent中起作用。
Background-K+ channel activation in vascular smooth muscle cells (VSMCs) plays a key role in regulating vascular tone. It has been proposed that endothelium-derived hyperpolarizing factor (EDHF) contributes to microvascular dilation more than nitric oxide (NO) does. Whether hyperpolarization is important for coronary arteriolar dilation in humans is not known. Bradykinin (BK), an endogenous vasoactive substance, is released from ischemic myocardium and regulates coronary resistance, Therefore, we tested the effects of inhibiting NO synthase, cyclooxygenase, and K+ channels on the changes in diameter and membrane potential (Em) in response to BK in isolated human coronary microvessels.Methods and Results-Arterioles (97 +/- 4 mu m: n = 120) dissected from human right atrial appendages (n = 78) were cannulated at a distending pressure of 60 mm Hg and zero flow. Changes in vessel diameter (video microscopy) and VSMC Em (glass microelectrodes) were measured simultaneously. In vessels constricted and depolarized (Em; -50 +/- 3 to -28 +/- 2 mV) with endothelin-1 (ET). dilation to BK was associated with greater membrane hyperpolarization (-48 +/- 3 mV at 10(-6) mol/L) than dilation to sodium nitroprusside (SNP) (-34 +/- 2 mV at 10(-4) mol/L) for similar degrees of dilation. Treatment with N-omega-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/L), an NO synthase inhibitor, partially decreased dilation to BK (maximum dilation 61 +/- 10% versus control 92 +/- 4%: P < 0.05), Charybdotoxin (CTX; 10(-8) mol/L). a large-conductance Ca2+-activated K+ channel blocker, ol apamin (10(-7) mol/L), a small-conductance Ca2+-activated K+ channel blocker, inhibited both dilation (CTX 22 +/- 6% and apamin 45 +/- 10% versus control 69 +/- 6%; P < 0.05) and membrane hyperpolarization (CTX -31 +/- 2 mV and apamin -37 +/- 2 mV versus control -44 +/- 2 mV; P < 0.05) to BK, whereas glibenclamide (10(-6) mol/L), an ATP-sensitive K+ channel blocker, was without effect.Conclusions-Vasodilation of human coronary arterioles to BK is largely dependent on membrane hyperpolarization by Ca2+-activated K+ channel activation, with apparently less of a role for endothelium-derived NO. This suggests a role for K+ channel activation in regulating human coronary arteriolar tent.