Sigma-1R overexpression in PVN deteriorated heart injury by upregulating sympathetic nerve tone

Abstract

Abstract Sympathetic nerve tone chronically maintains at high level is harmful to heart. However, little is known how to control sympathetic nerve tone. It has been reported that sigma-1 receptors played a multi-functional role in central nervous system diseases, but little is known about the function for adjusting sympathetic tone of sigma-1 receptors within paraventricular nucleus (PVN). We examined the effects of sigma-1 receptor within PVN on heart by two models: cardiopulmonary bypass model (CPB) and cirrhotic cardiomyopathy (CCM) induced by bile duct ligation. It was found that sigma-1R overexpression in PVN aggravated brain inflammation and increased sympathetic output with more serious heart change. Right stellate ganglion block alleviated the cardiac damage caused by Sigma-1R overexpression in PVN during CPB. In CCM model, it was found that overexpression of sigma-1 receptor in PVN promoted occurrence of fibrosis and senescence in heart. These findings suggest that sigma-1R overexpression in PVN deteriorate heart injury by upregulating sympathetic nerve tone.