Effects of coronary arterial reperfusion on beta-adrenergic receptor-adenylyl cyclase coupling.
Effects of coronary arterial reperfusion on beta-adrenergic receptor-adenylyl cyclase coupling.
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DOI：
10.1152/ajpheart.1993.264.1.h196
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
D. Vatner;K. Kiuchi;W. Manders;S. Vatner
中科院分区：
文献类型：
--
作者：
D. Vatner;K. Kiuchi;W. Manders;S. Vatner
在9只清醒犬上观察冠状动脉结扎(CAO)1h后再灌流(CAR)15min的效果。缺血通过缺血区局部血流量减少(放射性微球)和收缩节段性室壁运动丧失来证实。用~(125)I标记的氰基吲哚结合法测得粗膜组份中的β-肾上腺素能受体密度有下降的趋势，但无显著差异。然而，与非缺血的心内膜下组织相比，缺血的心内膜下组织的腺苷环化酶活性和鸟嘌呤核苷酸刺激蛋白(Gs)活性降低。缺血心内膜下和心外膜下，高亲和力的β-肾上腺素能受体结合激动剂的比例增加。与无CAO 1h的实验数据相比，CAR持续15min后，心肌缺血时β-受体密度的增加迅速逆转，而高亲和力受体结合激动剂的减少则逆转为高亲和力受体的增加。在单纯CAO中观察到的腺酰环化酶和Gs的整体降低持续存在，但在CAO后选择性地观察到先前缺血的心内膜下心肌。因此，CAO和CAR对β-肾上腺素能受体和腺苷环化酶的影响是不同的。在CAR期间，面对腺酰环化酶活性和Gs的持续降低，高亲和力的β-肾上腺素能受体结合激动剂的数量增加可能是一种代偿机制。
The effects of 1 h of coronary arterial occlusion (CAO) followed by 15 min reperfusion (CAR) were examined in nine conscious dogs. Ischemia was verified by decreased regional blood flow (radioactive microspheres) and loss of systolic regional wall motion in the ischemic zone. beta-Adrenergic receptor density assessed by 125I-labeled cyanopindolol binding in a crude membrane fraction tended to decrease but was not significantly different. However, adenylyl cyclase activity and the guanine nucleotide stimulatory protein (Gs) were reduced in ischemic subendocardium compared with nonischemic subendocardium. The fraction of beta-adrenergic receptors binding agonist with high affinity increased in ischemic subendocardial and subepicardial layers. Compared with prior data in experiments with 1 h CAO without CAR, the increase in beta-adrenergic receptor density that occurs with myocardial ischemia is rapidly reversed with CAR of 15 min duration, while the decreased fraction of receptors binding agonist with high affinity was reversed to an increase in high-affinity receptors. The global decreases in adenylyl cyclase and Gs, which have been observed with simple CAO, persist but are observed selectively in the previously ischemic subendocardium after CAR. Thus both CAO and CAR affect beta-adrenergic receptors and adenylyl cyclase differently. During CAR, increased numbers of beta-adrenergic receptors binding agonist with high affinity occur potentially as a compensatory mechanism in the face of persistent reductions in adenylyl cyclase activity and Gs.