The influence of inhibiting no formation on metabolic recovery of ischemic rat heart by Apelin-12

Abstract

Apelin 12 (A-12) was synthesized by the automatic solid phase method with use of Fmoc 'H-NMR spectroscopy and mass spectrometry. Effects of apelin-12 (a peptide comprised of 12 aminoacids, A-12) on recovery of energy metabolism and cardiac function were studied in isolated working rat hearts perfused with Krebs buffer (KB) containing 11 mM glucose that were subjected to global ischemia and reperfusion. A short-term infusion of μM 140 A-12 in KB prior to ischemia enhanced myocardial ATP, the total adenine nucleotide pool (EAN=ATP+ADP+AMP) and the energy charge of cardiomyocites ((ATP+0.5ADP+AMP) at the end of reperfusion compared with control (KB infusion) and reduced lactate content and lactate/pyruvate ratio in reperfused myocardium to the initial values. This effect was accompanied by improved recovery of coronary flow and cardiac function. Coadministration of 140 μM A-12 and 100 μM L-NAME (the nonspecific NOS inhibitor) profoundly attenuated the peptide influence on metabolic and functional recovery of reperfused hearts. The results indicate involvement of NO. formed under the peptide action, in mechanisms of cardioprotection that are tightly associated with recovery of energy metabolism in postischemic heart.