Phosphorylation of CaMK and CREB-Mediated Cardiac Aldosterone Synthesis Induced by Arginine Vasopressin in Rats with Myocardial Infarction

Int J Mol Sci. 2022 Dec 1;23(23):15061. doi: 10.3390/ijms232315061.

Abstract

Both aldosterone and arginine vasopressin (AVP) are produced in the heart and may participate in cardiac fibrosis. However, their relationship remains unknown. This study aims to demonstrate the regulation and role of AVP in aldosterone synthesis in the heart. Rats were subjected to a sham operation or myocardial infarction (MI) by ligating the coronary artery. Cardiac function and fibrosis were assessed using echocardiography and immunohistochemical staining, respectively. In addition, the effects of AVP stimulation on cardiac microvascular endothelial cells (CMECs) were studied using ELISA, real-time PCR, and Western blotting. Compared with the rats having undergone a sham operation, the MI rats had an increased LVMI, type I collagen composition, and concentrations of aldosterone and AVP in the heart but decreased cardiac function. As the MI rats aged, the LVMI, type I collagen, aldosterone, and AVP increased, while the LVMI decreased. Furthermore, AVP time-dependently induced aldosterone secretion and CYP11B2 mRNA expression in CMECs. The p-CREB levels were significantly increased by AVP. Nevertheless, these effects were completely blocked by SR49059 or partially inhibited by KN93. This study demonstrated that AVP could induce the secretion of local cardiac aldosterone, which may involve CaMK and CREB phosphorylation and CYP11B2 upregulation through V1 receptor activation.

Keywords: aldosterone; arginine vasopressin; fibrosis; heart failure; myocardial infarction; the adrenal cortex.

MeSH terms

  • Aldosterone / metabolism
  • Animals
  • Arginine Vasopressin* / metabolism
  • Arginine Vasopressin* / pharmacology
  • Collagen Type I
  • Endothelial Cells / metabolism
  • Fibrosis
  • Heart
  • Myocardial Infarction*
  • Rats

Substances

  • Arginine Vasopressin
  • Collagen Type I
  • Aldosterone