Nitric oxide synthase mediates the apelin-induced improvement of myocardial postischemic metabolic and functional recovery

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 Cterminal residue of apelin (A-12) and N G -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.

Apelin-12 and its structural analog enhance antioxidant defense in experimental myocardial ischemia and reperfusion

“…Traditionally they are attributed to mobilization of the PI3 K-Akt and MEK1/2-ERK1/2 salvage kinases, and inhibition of the mitochondrial permeability transition pore (mPTP) opening [7]. Phosphorylation and activation of endothelial nitric oxide synthase (eNOS) are also implicated in myocardial protection afforded by apelins [21,22]. Antioxidant properties of A12 and its analogs and ability of these peptides to scavenge reactive oxygen species (ROS) have not been studied so far.…”

Effects of structural analogues of apelin-12 in acute myocardial infarction in rats

“…However, abolishing or attenuating protective effects of apelin-13 and A12 after coadministration with N G -nitro-L-arginine methyl ester (L-NAME), the NOS inhibitor, directly indicate the principal role of NO. [1112] Since NO prevents mitochondrial oxygen damage and lipid peroxidation,[23] we may assume that reduction of I/R injury by A12 and analogue I might be related to antioxidant properties of these peptides. Such a possibility was recently confirmed by several authors for apelin-13.…”

“…[910] Phosphorylation and activation of endothelial nitric oxide synthase (eNOS) are also implicated in myocardial protection afforded by apelin. [61112] Recent clinical study revealed that plasma apelin concentration is reduced early after acute myocardial infarction and remains significantly low baseline at 24 weeks. [13] These facts strongly suggest that apelin administration may be promising in the treatment of coronary heart disease.…”

Effects of Exercise Combined With Apelin-13 on Cardiac Function in the Isolated Rat Heart

“…The main pathological manifestation of coronary artery disease as a cause of death worldwide is myocardial damage due to ischemia/ reperfusion (IR) injury. 1 In this regards many approaches to provide cardioprotection against IR induced injury have been studied. Until now, regular exercise has been agreed to be a pragmatic and sustainable countermeasure for cardioprotection.…”

“…11 Phosphorylation and activation of eNOS are also implicated in myocardial protection afforded by apelin. 1,12 These findings suggest that the beneficial effects of exercise and apelin are only in part overlapping and thus partly complementary and although both apelin and aerobic exercise training have been highly recommended to the treatment of heart failure (HF), it is unknown whether the combination of aerobic exercise training and apelin has integrative effects on the treatment of myocardial IR injuries. To date, to the best of our knowledge there are no studies testing the combined effect of these two therapeutic strategies on cardiac function.…”