Direct preconditioning of cardiac ventricular myocytes via adenosine A(1) receptor and K-ATP channel

被引:84
作者
Liang, BT
机构
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1996年 / 271卷 / 05期
关键词
hypoxia; cultured ventricular myocytes;
D O I
10.1152/ajpheart.1996.271.5.H1769
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Both adenosine receptor and ATP-sensitive K (K-ATP) channel mediate the protective effect of ischemic preconditioning in the intact heart. The objective of the present study was to determine the role of adenosine receptor and K-ATP channel as well as their interaction in simulating and mediating preconditioning of the cardiac myocyte. Cardiac ventricular myocytes cultured from chick embryos 14 days in ovo were developed as a myocyte model of preconditioning. Myocytes were preconditioned by exposing them to B-min hypoxia, termed preconditioning hypoxia, before a second 90-min hypoxia. Preconditioning resulted in a 64 +/- 3% decrease in the amount of creatine kinase released and a 66 +/- 2% reduction in the percentage of myocytes (+/-SE, n = 11) killed. Glibenclamide or 5-hydroxydecanoic acid (5-HD), when present during the preconditioning hypoxia, blocked the preconditioning effect. Prior exposure of the myocytes to pinacidil also led to a decrease in the injury sustained during the 90-min hypoxia. The protective effect of pinacidil was blocked by glibenclamide or 5-HD, suggesting that K-ATP channel activation can mimic as well as mediate preconditioning. Adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) blocked the protective effect of preconditioning hypoxia. Adenosine or the A(1) receptor agonist 2-chloro-N-G-cyclopentyladenosine (CCPA) can replace preconditioning hypoxia and mimic preconditioning; this effect was fully antagonized by 8-SPT, glibenclamide, or 5-HD. Adenosine A(1)-receptor activation caused a glibenclamide-sensitive inhibition of the basal Ca-45 influx and basal myocyte contractile amplitude, consistent with coupling of A(1) receptor to stimulation of K-ATP channel in the myocytes. The data provide direct evidence that myocyte K-ATP channel is the effector downstream from adenosine A(1) receptor in mediating the direct preconditioning of cardiac myocytes.
引用
收藏
页码:H1769 / H1777
页数:9
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