• Lovedeep Singh, Jasleen K Virdi, Leonid N Maslov, Nirmal Singh, and Amteshwar S Jaggi.
• Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
• Cardiovasc Ther. 2018 Jun 1; 36 (3): e12328.

BackgroundAdenosine is a breakdown product of adenosine triphosphate and plays an important role in pharmacological preconditioning. The cardioprotective effects of adenosine preconditioning are well established. However, the possible mechanisms need to be explored.AimThis study was aimed to investigate the possible mechanisms involved in adenosine preconditioning-induced cardioprotection in rats.MethodsRat heart was isolated and perfused on Langendorff apparatus. Global ischemia for 30 minutes followed by reperfusion for 120 minutes was employed to produce myocardial injury. Myocardial injury was assessed by measuring myocardial infarct size, release of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and hemodynamic parameters including left ventricular developed pressure (LVDP), dp/dtmax, and dp/dtmin . Serum nitrite levels were measured as an index of nitric oxide release in blood.ResultsAdenosine (4 mg/kg) preconditioning significantly decreased ischemia-reperfusion-induced increase in LDH, CK release, infarct size, improved LVDP, dp/dtmax and dp/dtmin, and increased serum nitrite levels. Pretreatment with L-NAME, a specific NOS inhibitor, (5 mg/kg) and montelukast, leukotriene receptor antagonist, (10 mg/kg) significantly abrogated the cardioprotective effect of adenosine preconditioning. However, seratrodast, thromboxane A2 antagonist, (15 mg/kg) had no effect on adenosine-induced cardioprotection. Sodium nitroprusside (SNP) preconditioning also produced cardioprotective effects. However, caffeine (20 mg/kg) (adenosine receptor blocker) and seratrodast (15 mg/kg) had no effect on SNP-induced cardioprotection. Administration of montelukast abrogated the cardioprotective effects of SNP preconditioning-induced cardioprotection.ConclusionAdenosine preconditioning may increase the release of nitric oxide, which in turn may increase the release of cysteinyl leukotrienes to confer cardioprotection.© 2018 John Wiley & Sons Ltd.

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