Mineralocorticoid and AT1 receptors in the paraventricular nucleus contribute to sympathetic hyperactivity and cardiac dysfunction in rats post myocardial infarct

摘要: Key points Central mineralocorticoid receptor (MR) and angiotensin II type 1 (AT1R) activation play a critical role in sympathetic hyperactivity progressive left ventricle (LV) remodelling dysfunction after myocardial infarction (MI). Intra-paraventricular nucleus (PVN) infusion of adeno-associated virus (AAV) carrying small interfering RNA (siRNA) against MR (AAV-MR-siRNA) markedly decreases both AT1R expression the PVN post MI, whereas AAV-AT1aR-siRNA only expression. Both AAVs largely prevent inhibit part LV MI. These findings indicate that enhanced MR–AT1R signalling is for contributes to MI. Abstract Intracerebroventricular or blocker rats attenuates ventricular (MI). The present study examined whether knockdown MRs AT1Rs specifically paraventricular these effects, compared cardiac effects with those systemic treatment β1-adrenergic metoprolol. was infused either (AAV-AT1R-siRNA), as control scrambled siRNA. At 4 weeks but not increased PVN, excitatory renal nerve activity pressor responses air stress were enhanced, arterial baroreflex function impaired; end-diastolic pressure (LVEDP) peak systolic (LVPSP), ejection fraction (EF) dP/dtmax decreased. AAV-MR-siRNA AAV-AT1R-siRNA normalized similarly ameliorated stress, prevented desensitization, improved LVEDP, EF well interstitial (but perivascular) fibrosis. In second set rats, metoprolol at 70 250 mg kg−1 day−1 drinking water MI did improve except decrease LVEDP lower dose. These results suggest MR-dependent upregulation hyperactivity, MI. normalizing more effective strategy than β1 blockade.