title: Cardioprotective effect with carbon monoxide releasing molecule-2 (CORM-2) in isolated perfused rat heart: Role of coronary endothelium and underlying mechanism.
abstract: 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 30microM/l and 50microM/l of CORM-2 for 10min 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 100microM CORM-2. We observed that pretreatment with L-NAME (100microM/l), a nitric oxide synthase (NOS) inhibitor did not affect protection by CORM-2 (50microM/l). On the other hand pretreatment with Triton X-100 (0.05% for 20s) to denude endothelium before CORM-2 treatment followed by I/R injury showed similar cardioprotection. Moreover, pretreatment with K(ATP) 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 K(ATP) channel present on vascular smooth muscle cell (VSMC).
authors.affiliation: Zydus Research Centre (ZRC communication no. # 302), Sarkhej-Bavla N.H 8A Moraiya, Ahmedabad-382210, India.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Soni
authors.forename: Praful
authors.initials: P
authors.lastname: Patel
authors.forename: Akshyaya C
authors.initials: AC
authors.lastname: Rath
authors.forename: Mukul
authors.initials: M
authors.lastname: Jain
authors.forename: Anita A
authors.initials: AA
authors.lastname: Mehta
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D054086:KATP Channels; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase