Effect of the changes of NMDA receptor in hypothalamic paraventricular nucleus on cardiac function and sympathetic nervous activity in rats with heart failure

摘要

Abstract Objective To observe the effect of the changes of n-methyl- d -aspartate receptor 1 (NMDAR1), tyrosine hydroxylase (TH), and glutamic acid decarboxylase 67 (GAD67) in the hypothalamic paraventricular nucleus (PVN) on cardiac function and sympathetic nervous activity in rats with heart failure (HF). Methods Thirty-six adult male SD rats were randomly divided into the heart failure group (HF), the heart failure?+?NMDA receptors agonist AP5 intervention group (HF-AP5), and the Sham-operation group (SO) (n?=?12). HF model in SD rats was induced by ligation of left coronary artery. AP5 (0.02?μg/h) was administrated by the paraventricular nucleus subsequently for 4 weeks. The cardiac function, renal sympathetic nerve activity (RSNA), lung/body weight ratio (L/BW), and right ventricle/body weight ratio (RV/BW), as well as the plasma noradrenaline (NE) and Angiotensin II (Ang II) level and the expressions of NMDAR1, GAD67, and TH in PVN, in different groups were recorded 4 weeks after the establishment of HF model. Results After the coronary artery was ligated, LVEDP was increased, ±dp/dt max and LVEF were decreased, lung/BW and RV/BW were raised. RSNA, Ang II and NE were raised. Expression of NMDAR1 and TH were increased, but GAD67 was decreased. The levels of LVEDP, lung/BW, and RV/BW in group HF-AP5 were reduced while?±?dp/dtmax was increased after the treatment. The blood Ang II and NE content was decreased, RSNA was reduced, expression of NMDAR1 and TH were downregulated, but GAD67 was upregulated. Conclusions NMDAR1 is significantly activated in PVN of HF rats, the activity of TH is increased, GAD67 is downregulated, RSNA is increased, and the heart function is decreased. NMDA receptor blockers can alleviate HF. Highlights ? NMDAR1 is activated in PVN of HF rats. ? Injection of the NMDAR receptor agonist AP5 into the PVN can alleviate HF in the rat model. ? PVN could be a new direction in studying the mechanism of HF.