Apelin‑13 in the paraventricular nucleus (PVN) attenuates myocardial ischemia through V1a receptors in PVN/nucleus tractus solitarii (NTS) and GARγ2 in NTS.

Abstract

The apelin system plays a significant role in central blood pressure regulation, but its role in the neural control of myocardial protection remains poorly understood. The present study evaluated the effects of apelin‑13 in the paraventricular nucleus (PVN) on myocardial infarction (MI). In a male rat MI model, apelin‑13 expression was decreased in PVN, while Vasopressin 1a (V1a) receptor expression was increased in both PVN and nucleus tractus solitarii (NTS) and GABAA receptor (GAR)γ2 expression was increased in NTS. Cardiac function was assessed after microinjection of apelin‑13 or gene transfer of apelin‑13 into the PVN. Apelin‑13 overexpression in PVN markedly improved MI cardiac function, as evidenced by left ventricular end‑diastolic diameter, left ventricular end‑systolic diameter, left ventricular ejection fraction and left ventricular fractional shortening, along with decreased plasma noradrenaline and increased vasopressin levels. Mechanistically, both TGF‑β/Smad signaling and Bax/Bcl‑2 expression were implicated in heart tissue. Additionally, serum levels of four parasympathetic neuropeptides (somatostatin, cholecystokinin, glucagon‑like peptide‑1 and vasoactive intestinal peptide) were elevated in parallel with cardiac function improvement. Notably, V1a receptor antagonist administration in PVN/NTS or GAR agonist treatment in NTS attenuated the cardioprotective effects of apelin‑13. These findings demonstrated that PVN apelin‑13 overexpression improves cardiac function through V1a receptors (PVN/NTS) and GARγ2 (NTS), involving both parasympathetic neuroendocrine activation and modulation of myocardial apoptotic/inflammatory pathways. The present study provided novel insights into neural mechanisms of cardiovascular regulation.