Investigating the possible mechanisms involved in adenosine preconditioning-induced cardioprotection in rats

Background: Adenosine 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. Aim: This study was aimed to investigate the possible mechanisms involved in adenosine preconditioning-induced cardioprotection in rats. Methods: Rat heart was isolated and perfused on Langendorff apparatus. Global ischemia for 30minutes followed by reperfusion for 120minutes 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/dt(max,) and dp/dt(min). Serum nitrite levels were measured as an index of nitric oxide release in blood. Results: Adenosine (4mg/kg) preconditioning significantly decreased ischemia-reperfusion-induced increase in LDH, CK release, infarct size, improved LVDP, dp/dt(max) and dp/dt(min,) and increased serum nitrite levels. Pretreatment with L-NAME, a specific NOS inhibitor, (5mg/kg) and montelukast, leukotriene receptor antagonist, (10mg/kg) significantly abrogated the cardioprotective effect of adenosine preconditioning. However, seratrodast, thromboxane A(2) antagonist, (15mg/kg) had no effect on adenosine-induced cardioprotection. Sodium nitroprusside (SNP) preconditioning also produced cardioprotective effects. However, caffeine (20mg/kg) (adenosine receptor blocker) and seratrodast (15mg/kg) had no effect on SNP-induced cardioprotection. Administration of montelukast abrogated the cardioprotective effects of SNP preconditioning-induced cardioprotection. Conclusion: Adenosine preconditioning may increase the release of nitric oxide, which in turn may increase the release of cysteinyl leukotrienes to confer cardioprotection.