The role of inhibition of NO formation in the metabolic recovery of ischemic rat heart by apelin-12

Abstract

The effects of apelin 12, a 12 amino acid peptide (H Arg Pro Arg Leu Ser His Lys Gly Pro Met Pro Phe OH, A 12), on recovery of energy metabolism and cardiac function have been studied in iso lated working rat hearts perfused with Krebs buffer (KB) containing 11 mM glucose and subjected to global ischemia and reperfusion. Infusion of 140 μM A 12 before ischemia enhanced myocardial ATP, the total pool of adenine nucleotides (ΣAN = ATP+ADP+AMP) and the energy charge of cardiomyocytes ((ATP + 0.5ADP)/ΣAN) at the end of reperfusion compared with control (KB infusion) and decreased lactate content and lactate/pyruvate ratio in the reperfused myocardium up to the initial values. This was accompanied by improved recovery of coronary flow and cardiac function. Co administration of A 12 and 100 μM L NAME (an inhibitor of NO synthases) significantly attenuated the A 12 effects on metabolic and functional recovery of reperfused hearts. These results indicate involvement of NO in mechanisms of cardioprotection that are tightly associated with recovery of energy metabolism in the postischemic heart.