BLOCKADE OF THE ATP-SENSITIVE POTASSIUM CHANNEL MODULATES REACTIVE HYPEREMIA IN THE CANINE CORONARY CIRCULATION
BLOCKADE OF THE ATP-SENSITIVE POTASSIUM CHANNEL MODULATES REACTIVE HYPEREMIA IN THE CANINE CORONARY CIRCULATION
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DOI：
10.1161/01.res.69.3.618
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发表时间：
1991-09-01
影响因子：
20.1
通讯作者：
SILVERMAN, H
中科院分区：
文献类型：
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作者：
AVERSANO, T;OUYANG, P;SILVERMAN, H
反应性充血的机制尚不清楚。我们假设反应性充血与冠状动脉闭塞时ATP敏感性钾通道的开放有关。平滑肌细胞质膜的超极化可能减少通过电压依赖性钙通道的钙内流，并导致平滑肌张力松弛和血管舒张。在8只开胸麻醉的狗中，30秒的冠状动脉闭塞导致平均200 +/-41%的债务偿还。冠状动脉内输注低剂量（0.8 μ mol/min）和高剂量（3.7 μ mol/min）格列本脲后，血流债偿还率分别下降至76 +/- 14%和50 +/-8%（与对照组相比，p < 0.05）。血流债偿还的下降是由于反应性充血期间最大冠状动脉电导及其持续时间的显著减少。此外，格列本脲给药后，冠状循环对腺苷诱导的血管舒张的敏感性显著下降。虽然变异性更大，但格列本脲给药后，冠状动脉血管对乙酰胆碱诱导的血管舒张的敏感性总体上没有变化。我们得出的结论是，反应性充血在很大程度上是由ATP敏感性钾通道决定的，可能是通过其对膜电位和电压敏感性钙通道的影响。由于在试验的最高剂量格列本脲下反应性充血从未完全消除，因此可能在这种复杂现象的发生中涉及其他机制。
The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average How debt repayment of 200 +/- 41%. After low-dose (0.8-mu-mol/min) and high-dose (3.7-mu-mol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 +/- 14% and 50 +/- 8%, respectively (p < 0.05 compared with control for both). The decline in flow debt repayment was due to a significant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon.