Role of Sigma-1 Receptors in the Paraventricular Nucleus and Myocardium during Cirrhotic Cardiomyopathy in Rats.

This study aims to investigate the alterations in Sigma-1 receptor (Sigma-1R) expression in the paraventricular nucleus (PVN) of the hypothalamus and in the myocardium during the development of bile duct ligation-induced cirrhotic cardiomyopathy (CCM) in rats. Furthermore, we sought to determine the impact of Sigma-1R overexpression in the PVN on the progression of CCM and its potential associations with sympathetic nervous system activity and endoplasmic reticulum stress. Additionally, changes in dopamine D1 receptor (D1R) expression in CCM were examined. Our findings indicate that CCM is associated with upregulated Sigma-1R expression in both the PVN and myocardium, as well as with excessive endoplasmic reticulum stress in the hypothalamic PVN and myocardial tissue, along with increased peripheral sympathetic activity. Overexpression of Sigma-1R in the PVN exacerbates CCM, likely through enhancing endoplasmic reticulum stress within the PVN and increasing central and peripheral sympathetic outflow. Moreover, CCM is also linked to upregulation of D1R in both central and cardiac regions. These results suggest that Sigma-1R may modulate central sympathetic output via D1R signaling, thereby influencing the pathogenesis and progression of CCM.