Apelin-13 in the paraventricular nucleus protects myocardium from ischemia via V1a receptor of the paraventricular nucleus and GABAA receptor γ2 of the nucleus tractus solitarii in rats

Abstract

BackgroundApelin system plays a significant role in central blood pressure regulation, but its role in neural control of myocardial injury protection is poorly understood. Thus, this study was undertaken to evaluate the effects of apelin-13 in the paraventricular nucleus (PVN) on myocardial infarction (MI) and ischemia/reperfusion (I/R). MethodsThe cardiac functions were assessed after microinjecting or transferring the apelin-13 gene into the paraventricular nucleus (PVN) of rat models with myocardial infarction (MI) or ischemia/reperfusion (I/R). ResultsIn MI rats, we showed that apelin-13 expression decreased in PVN, V1a receptor expression increased in PVN and nucleus tractus solitarii (NTS), and GABAA receptor (GAR) {gamma}2 expression increased in NTS. In primary cultured hypothalamus and medulla oblongata neurons, V1a receptor expression was downregulated by APJ receptor antagonist or GAR agonist, indicating that there are interactions between these receptors in neurons. Apelin-13 overexpression in PVN significantly improved cardiac function of MI and I/R rats, including left-ventricular end-diastolic diameter, left-ventricular end-systolic diameter, left-ventricular ejection fraction, and left-ventricular fractions shortening, accompanied by decreased noradrenaline and increased vasopressin plasma levels. Myocardial ischemia-related apoptotic and inflammatory pathway markers (Bcl-1, Bax, TGF-{beta}1, CCR5, Smad2) were downregulated and four neuropeptides of the parasympathetic endocrine system (somatostatin, cholecystokinin, glucagon-like peptide 1, vasoactive intestinal peptide) were increased in serum correspondingly with cardiac function improving. V1a receptor antagonist in PVN or NTS and GAR agonist in NTS decreased the effects of apelin-13 overexpression on cardiac function of MI and I/R rats. ConclusionsOverexpression of apelin-13 in PVN leads to cardiac function improvement via V1a receptor in PVN and NTS, and GAR{gamma}2 in NTS. Parasympathetic endocrine system and myocardial ischemia-related apoptotic and inflammation signaling pathways are involved in apelin-13 in PVN-mediated cardiac function regulation, which provides evidence for neural regulation of cardiovascular diseases.