Bradykinin mediation of Ca(2+)-activated K+ channels regulates coronary blood flow in ischemic myocardium.
Bradykinin mediation of Ca(2+)-activated K+ channels regulates coronary blood flow in ischemic myocardium.
复制标题
Ca(2) 激活的 K 通道的缓激肽介导可调节缺血心肌中的冠状动脉血流。
作者：
K. Node;M. Kitakaze;H. Kosaka;T. Minamino;M. Hori
背景
内皮依赖性超极化因子通过开放Ca（2+）激活的K+（KCa）通道来松弛血管平滑肌。本文研究了心肌缺血时KCa通道开放在冠状动脉舒张中的作用。
方法和结果
通过颈动脉体外转流管，对开胸犬的冠状动脉左前降支进行血液灌注。冠状动脉内给药缓激肽增加犬的冠状动脉血流量（CBF）与NG-硝基-L-精氨酸甲酯（L-NAME），一氧化氮合酶的抑制剂，这种效果完全抑制KCa通道阻滞剂伊比利亚毒素。在用L-NAME治疗的狗中，旁路管被堵塞以将CBF降低到基线值的三分之一，之后冠状动脉灌注压保持恒定。在冠状动脉灌注不足期间，冠状动脉内给予伊比利亚毒素20分钟进一步降低CBF（从33 +/- 2降至19 +/- 2 mL.100 g-1.min-1，P < .01）、缩短分数和乳酸提取率。缓激肽释放，缓激肽受体拮抗剂HOE-140阻断了伊比利亚毒素对心肌缺血期间冠状动脉血流动力学和代谢参数的影响。虽然L-NAME和腺苷受体拮抗剂8-磺苯基茶碱的组合减少了冠状动脉闭塞20秒后的反应性充血流量，但另外存在的伊比利亚毒素导致该参数进一步降低。
结论
在开胸犬心肌缺血时，内源性缓激肽引起的KCa通道开放有助于冠状动脉血管舒张，减少收缩和代谢功能障碍。
BACKGROUND
Endothelium-dependent hyperpolarizing factor relaxes vascular smooth muscles by opening the Ca(2+)-activated K+ (KCa) channels. The role of the opening of KCa channels in coronary vasodilation during myocardial ischemia was investigated.
METHODS AND RESULTS
The left anterior descending coronary arteries of open-chest dogs were perfused with blood through an extracorporeal bypass tube from the carotid artery. Intracoronary administration of bradykinin increased coronary blood flow (CBF) in dogs treated with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; this effect was completely inhibited by the KCa channel blocker iberiotoxin. In dogs treated with L-NAME, the bypass tube was occluded to reduce CBF to one third of the baseline value, after which coronary perfusion pressure was maintained constant. Intracoronary administration of iberiotoxin for 20 minutes further decreased CBF (from 33 +/- 2 to 19 +/- 2 mL.100 g-1.min-1, P < .01), fractional shortening, and lactate extraction ratio during coronary hypoperfusion. Bradykinin was released, and the bradykinin receptor antagonist HOE-140 blocked the effects of iberiotoxin on coronary hemodynamic and metabolic parameters during myocardial ischemia. Although the combination of L-NAME and the adenosine receptor antagonist 8-sulfophenyltheophylline reduced reactive hyperemic flow after 20 seconds of coronary occlusion, the additional presence of iberiotoxin resulted in a further decrease in this parameter.
CONCLUSIONS
The opening of KCa channels in response to endogenous bradykinin contributed to coronary vasodilation and reduced contractile and metabolic dysfunction during myocardial ischemia in open-chest dogs.
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缓激肽在心脏过敏反应中的保护作用。
影响因子：
20.1
作者：
Rubin,LE;Levi,R
通讯作者：
Levi,R
影响因子：
20.1
作者：
MOMBOULI, JV;ILLIANO, S;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM
一氧化氮是缺氧冠状血管舒张的介质。
影响因子：
20.1
作者：
Park,KH;Rubin,LE;Gross,SS;Levi,R
通讯作者：
Levi,R
DOI：
--
发表时间：
1987-03
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
A. Pinto;N. Abraham;K. Mullane
通讯作者：
A. Pinto;N. Abraham;K. Mullane