Cardioprotective effect with carbon monoxide releasing molecule-2 (CORM-2) in isolated perfused rat heart: Role of coronary endothelium and underlying mechanism
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- 作者：Hitesh Soni ; Praful Patel ; Akshyaya C Rath ; Mukul Jain ; Anita A Mehta
- 关键词：Carbon monoxide releasing molecule-2 ; Cardioprotection ; Coronary endothelium ; Vascular smooth muscle cell ; KATP channel
- 刊名：Vascular Pharmacology
- 出版年：2010
- 出版时间：July-August 2010
- 年：2010
- 卷：53
- 期：1-2
- 页码：68-76
- 全文大小：1806 K
文摘
Although the cardioprotective role of carbon monoxide (CO) has been studied against myocardial ischemia-reperfusion (I/R) injury, the role of coronary endothelium and underlying mechanism in carbon monoxide-induced cardioprotection is not well understood in isolated heart. The present study was designed to determine the role of coronary endothelium in CORM-2-mediated cardioprotection during I/R injury in isolated rat heart. Preconditioning with 30 µM/l and 50 µM/l of CORM-2 for 10 min markedly reduced lactate dehydrogenase (LDH) and creatinin kinase (CK) levels in coronary effluent after global ischemia. There was also a significant improvement in coronary flow rate, heart rate, cardiodynamic parameters and marked attenuation in infarct size. However, protective effect was abolished when hearts were pretreated with 100 µM CORM-2. We observed that pretreatment with L-NAME (100 µM/l), a nitric oxide synthase (NOS) inhibitor did not affect protection by CORM-2 (50 µM/l). On the other hand pretreatment with Triton X-100 (0.05 % for 20 s) to denude endothelium before CORM-2 treatment followed by I/R injury showed similar cardioprotection. Moreover, pretreatment with KATP channel inhibitor, glibenclamide almost completely reversed the cardioprotective effect of CORM-2 in endothelium-denuded hearts. These results indicate that cardioprotection by CORM-2 is highly concentration-dependent, independent of coronary endothelium and cardioprotective effect might be attributed to the activation of KATP channel present on vascular smooth muscle cell (VSMC).