科研之友
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摘要
Angiotensin-converting enzyme inhibitors and angiotensin AT(1) receptor blockers reduce myocardial ischemia-reperfusion injury via bradykinin B-2 receptor- and angiotensin AT(2) receptor-mediated mechanisms. The renin inhibitor aliskiren increases cardiac tissue kallikrein and bradykinin levels. In the present study, we investigated the effect of aliskiren on myocardial ischemia-reperfusion injury and the roles of B-2 and AT(2) receptors in this effect. Female Sprague-Dawley rats were treated with aliskiren (10 mg/kg per day) and valsartan (30 mg/kg per day), alone or in combination, together with the B-2 receptor antagonist icatibant (0.5 mg/kg per day) or the AT(2) receptor antagonist PD123319 (30 mg/kg per day), for 4 weeks before myocardial ischemia-reperfusion injury. Aliskiren increased cardiac bradykinin levels and attenuated valsartan-induced increases in plasma angiotensin II levels. In vehicle-treated rats, myocardial infarct size (% area at risk, mean +/- SEM, n=7-13) was 43 +/- 3%. This was reduced to a similar extent by aliskiren, valsartan, and their combination to 24 +/- 3%, 25 +/- 3%, and 22 +/- 2%, respectively. Icatibant reversed the cardioprotective effects of aliskiren and the combination of aliskiren plus valsartan, but not valsartan alone, indicating that valsartan-induced cardioprotection was not mediated by the B-2 receptor. PD123319 reversed the cardioprotective effects of aliskiren, valsartan, and the combination of aliskiren plus valsartan. Aliskiren protects the heart from myocardial ischemia-reperfusion injury via a B-2 receptor- and AT(2) receptor-mediated mechanism, whereas cardioprotection by valsartan is mediated via the AT(2) receptor. In addition, aliskiren attenuates valsartan-induced increases in angiotensin II levels, thus preventing AT(2) receptor-mediated cardioprotection by valsartan.
- 出版日期2014-4
- 单位河北医科大学
