Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition against ischemic myocardial injury

被引:23
作者
Node, K
Kitakaze, M
Kosaka, H
Minamino, T
Mori, H
Hori, M
机构
[1] Osaka Univ, Sch Med, Dept Med 1, Suita, Osaka 565, Japan
[2] Osaka Univ, Sch Med, Dept Physiol, Suita, Osaka 565, Japan
[3] Tokai Univ, Sch Med, Dept Physiol, Isehara, Kanagawa 25911, Japan
关键词
angiotensin-converting enzyme; nitric oxide; potassium channels; prostacyclin; bradykinin; infarction;
D O I
10.1161/01.HYP.31.6.1290
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Angiotensin-converting enzyme (ACE) inhibitors increase the production of nitric oxide (NO) and prostacyclin and open Ca2+-activated K+ channels. The effects of these actions of ACE inhibitors on infarct size were investigated in open-chest dogs subjected to myocardial ischemia and reperfusion. Infarct size was assessed 6 hours after the onset of reperfusion, subsequent to 90 minutes of occlusion of the left anterior descending coronary artery. The ACE inhibitor cilazaprilat was administered into the coronary artery 10 minutes before coronary occlusion, and infusion was continued until 1 hour after reperfusion. The bradykinin and NO concentrations in coronary venous blood 10 minutes after the onset of reperfusion were significantly higher in dogs treated with cilazaprilat (3 mu g.kg(-1).min(-1)) than in control animals. Although there were no significant differences in collateral flow during ischemia, infarct size in the cilazaprilat group was smaller than that in the control group (15.1+/-3.0% versus 46.7+4.2% of the area at risk, P<0.0001), The infarct size-limiting effect of cilazaprilat was partially reduced by either NG-nitro-L-arginine methyl ester tan inhibitor of NO synthase) or iberiotoxin (a blocker of Ca2+-activated K+ channels) and was abolished by NG-nitro-L-arginine methyl ester plus iberiotoxin. Indomethacin tan inhibitor of cyclooxygenase) had no effect on the beneficial action of cilazaprilat. Inhibition of ACE thus reduced myocardial infarct size, an effect that was mediated by NO and the opening of Ca2+-activated K+ channels in canine hearts.
引用
收藏
页码:1290 / 1298
页数:9
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