INVOLVEMENT OF NITRIC OXIDE DEPENDENT MECHANISM IN APELIN ACTION ON MYOCARDIAL ISCHEMIA/REPERFUSION INJURY IN MALE ALBINO RATS

Abstract

Background: Apelin acts as a regulating peptide of cardiovascular, hypothalamus, hypophysis, metabolic, gastrointestinal and immune systems. Objective: The goal of this study was to clarify whether apelin-13 is cardioprotective against ischemia/reperfusion injury if given as either a pre- or postconditioning mimetic and whether nitric oxide (NO) is involved in apelin-induced protection. Design: Langendorff perfused rat hearts underwent 30 min of global ischemia and 120 min of reperfusion. Infarct size and lactate dehydrogenase, creatine kinase –MB and malondialdehyde release were determined to evaluate the severity of myocardial injury. Apelin-13 was infused at 0.5 μM concentration for 20 min either before ischemia or in early reperfusion, without and with NO synthase inhibition by NG-nitro-L-arginine –methyl ester (L-NAME). In additional experiments, before ischemia also 1 μM apelin-13 was tested. Results: Whereas before ischemia apelin-13 (0.5 and 1.0 μM) was ineffective, after ischemia it reduced infarct size, lactate dehydrogenase, creatine kinase –MB and malondialdehyde release when compared with control group (P<0.001). In addition, it could be noticed that the cardioprotective effect of apelin was abolished in the presence of L-NAME, а nonspecific NOS inhibitor. Conclusion: Apelin-13 protects the heart only if given after ischemia. In this protection NO plays an important role. Further studies are recommended on the endogenous origin and the mode of action of apelin-13 within the pool of treatments under study for postinfarction therapy as well as the use of markers for NO detection, and selective inhibitors of NOS for further delineation of apelin effects on ischemic myocardium. Key words: Apelin, ischemia/ reperfusion injury, nitric oxide.