Abstract
The adipocytokine apelin is capable to reduce myocardial ischemia/reperfusion injury in rodents. Cardioprotective activity of apelin may be attributed to upregulation of endothelial nitric oxide synthase (eNOS). This study was designed to examine metabolic and functional effects of a synthesized 12 C-terminal residue of apelin (A-12) and NG-nitro-L-arginine methyl ester (L-NAME), a non-selective eNOS inhibitor, in isolated working rat hearts subjected to global ischemia. Preischemic infusion of A-12 increased recovery of cardiac function during reperfusion compared with control and resulted in enhanced restoration of myocardial ATP, adenine nucleotide pool, phosphocreatine and reduction of myocardial lactate and lactate/pyruvate ratio. Coadministration of A-12 and L-NAME aggravated recovery of coronary flow and cardiac function compared with these indices after A-12 treatment. Cardiac dysfunction was associated with increase in lactate dehydrogenase release in myocardial effluent, reduction of glucose oxidation and abolishment of augmented restoration of high energy phosphates. The results clearly demonstrate involvement of NOS-dependent mechanisms in cardioprotection afforded by apelin.
Highlights
The development of new approaches to protection of the myocardium against ischemia/reperfusion (I/R) injury is an actual objective of experimental cardiology
It is known that the myocardium is the source of endogenous protective mechanisms that are stimulated in ischemia and reperfusion
The control group showed substantially reduced coronary flow, the LVDP × HR product (a) and cardiac output compared with the baseline values; in addition, coronary resistance increased to 121% ± 2% (p < 0.01)
Summary
The development of new approaches to protection of the myocardium against ischemia/reperfusion (I/R) injury is an actual objective of experimental cardiology. Reperfusion of an ischemic myocardium results in altered cardiac energy metabolism, which in turn may contribute to delayed functional recovery [1]. Interventions that improve the transition from anaerobic to aerobic myocardial metabolism (insulin, adenosine and certain amino acids) facilitate the recovery of oxidative phosphorylation and left ventricular function during postischemic reperfusion [2,3]. Phosphorylation and activation of endothelial nitric oxide synthase (eNOS), a key target of apelin, lead to formation of NO which is involved in diverse mechanisms of cellular protection, including inhibition of the mPTP opening [18,19]. Apelin-13 promoted eNOS expression in parallel with activation of Akt and ERK1/2 path-
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