Involvement of nitric oxide in cardioprotective effect of endothelin receptor antagonist during ischemia-reperfusion

被引:44
作者
Gourine, AV [1 ]
Gonon, AT [1 ]
Pernow, J [1 ]
机构
[1] Karolinska Hosp, Dept Cardiol, S-17176 Stockholm, Sweden
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2001年 / 280卷 / 03期
关键词
reperfusion injury;
D O I
10.1152/ajpheart.2001.280.3.H1105
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The interaction between the cardioprotective effect of endothelin (ET) receptor blockade and nitric oxide (NO) during ischemia-reperfusion injury was investigated. Anesthetized pigs were subjected to 45 (protocol 1) or 30 min (protocol 2) coronary artery ligation and 4 h reperfusion. In protocol 1, five groups were given vehicle, the ETA receptor antagonist LU-135252 (LU), the NO synthase (NOS) inhibitor N-G-nitro-L-arginine (L-NNA), L-NNA in combination with LU, or L-NNA in combination with the NO precursor L-arginine (L-Arg) and LU intravenously before ischemia. In protocol 2, two groups were given vehicle or L-NNA. In protocol 1, the infarct size (IS) was 79 +/- 5% of the area at risk in the vehicle group and 93 +/- 2% in the L-NNA group. LU reduced the IS to 43 +/- 7% (P < 0.001). The cardioprotective effect of LU was abolished in the presence of L-NNA (IS 76 +/- 6%), whereas addition of L-Arg restored its cardioprotective effect (IS 56 +/- 2%; P < 0.05 vs. vehicle and L-NNA 1 LU groups). In protocol 2, the IS was 49 +/- 6% in the vehicle group and 32 +/- 4% in the L-NNA group (P = not significant). Myocardial ET-like immunoreactivity (ET-LI) increased in the vehicle group of protocol 1. ET-LI in the ischemic-reperfused myocardium was lower in the groups given LU (P < 0.01) and L-NNA + L-Arg + LU (P < 0.05) but not in the group given L-NNA + LU compared with the vehicle group. These results suggest that the cardioprotective effect of the ETA receptor antagonist is mediated via a mechanism related to NO.
引用
收藏
页码:H1105 / H1112
页数:8
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