Chronic sigma-1 receptor activation ameliorates ventricular remodeling and decreases susceptibility to ventricular arrhythmias after myocardial infarction in rats.

Abstract

The present study aimed to assess the effect of sigma-1 receptor (S1R) stimulation on ventricular remodeling and susceptibility to ventricular arrhythmias (VAs) after myocardial infarction (MI) in rats. Wild-type male rats were placed into one of the following four treatment groups. For four weeks, animals in the Sham group and MI group received intraperitoneal (i.p.) injections of 0.9% saline (1 ml/kg/day); those in the MI + F group received fluvoxamine (FLV) (0.3 mg/kg/day); and those in the MI + F + BD group received FLV plus BD1047 (0.3 mg/kg/day). After that, the ventricular electrophysiological parameters were measured via the langendorff system. Ventricular fibrosis quantification was determined with Masson staining. Cardiac function was evaluated by echocardiography. The protein levels of S1R, connexin (Cx)43, Cav1.2, Kv4.2, Kv4.3, tyrosine hydroxylase (TH), nerve growth factor (NGF), growth-associated protein 43 (GAP43) were detected by Western blot assays. Our results indicated that fluvoxamine significantly prolonged the ventricular effective refractory period (ERP), shortened action potential duration (APD), reduced susceptibility to VAs after MI. Masson staining showed a decrease in ventricular fibrosis in the MI + F group. Furthermore, the contents of Cx43, S1R, Cav1.2, Kv4.2, Kv4.3 were increased in the MI + F group compared with the MI group (all P < 0.05). The contents of TH, NGF, GAP43 were reduced in the MI + F group compared with the MI group. (all P < 0.05). However, BD1047 reduces all of these effects of FLV. The results suggest that S1R stimulation reduces susceptibility to VAs and improves cardiac function by improving myocardial fibrosis, lightning sympathetic remodeling, electrical remodeling, gap junction remodeling and upregulating S1R content.

• Authors: Yuhong Fo, Cui Zhang, Xiuhuan Chen, Xin Liu, Tianxin Ye, Yan Guo, Chuan Qu, Shaobo Shi, Bo Yang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 889 Pg. 173614 (Dec 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 33010304 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Receptors, sigma
• Fluvoxamine

Topics

• Animals
• Drug Administration Schedule
• Fluvoxamine (administration & dosage)
• Male
• Myocardial Infarction (complications, drug therapy, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, sigma (agonists, metabolism)
• Ventricular Fibrillation (etiology, metabolism, prevention & control)
• Ventricular Remodeling (drug effects, physiology)
• Sigma-1 Receptor