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 1H-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 (ΣAN=ATP+ADP+AMP) and the energy charge of cardiomyocites ((ATP+0.5ADP)/ΣAN) 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.

Apelin Is a Prototype of Novel Drugs for the Treatment of Acute Myocardial Infarction and Adverse Myocardial Remodeling

“…Intravenous administration of apelin-12 at a dose of 0.07 µmol/kg (0.1 mg/kg) reduced infarct size by 21%, at a dose of 0.35 µmol/kg (0.5 mg/kg) by 34% in reperfusion [ 34 ]. It was found that apelin-12 at a dose of 0.35 µmol/kg (0.5 mg/kg, intravenously) reduced infarct size by 40% in rats with reperfusion of the heart after CAO (40 min) [ 44 ]. Apelin-12 reduced infarct size by 33% at a dose of 0.7 µmol/kg (1 mg/kg).…”

“…It was demonstrated that NO-synthase is involved in the cardioprotective effect of apelin-12 in the reperfusion of the heart both in vivo and in vitro [ 43 , 44 ]. Infusion of apelin-13 (0.5 µmol/L) protects isolated rat hearts against reperfusion injury [ 45 ].…”

The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction

“…Furthermore, NO formation is involved in the process of recovery of energy metabolism induced by the apelin/APJ system. Restoration of energy metabolism increases functional recovery of the heart and decreases cell membrane damage in MIRI [147,148].…”