Abstract
C‑type natriuretic peptide (CNP), from the family of natriuretic peptides (NPs), has been shown to induce antihypertrophic and antifibrotic effects in cardiomyocytes. However, the roles of CNP in the atrial dysregulation of connexin (Cx)40 and Cx43 remain to be elucidated. The present study aimed to investigate the effects of CNP on angiotensin (Ang) II‑induced Cx40 and Cx43 dysregulation in isolated perfused beating rat left atria. A rat isolated perfused beating atrial model was used and the protein levels were determined via western blotting. Ang II significantly upregulated NF‑κB, activator protein‑1, transforming growth factor‑β1 (TGF‑β1), collagen I and matrix metalloproteinase 2, leading to atrial fibrosis, and downregulated expression of Cx40 and Cx43. The changes in Cx40 and Cx43 induced by Ang II were abolished by CNP through upregulation of phosphorylated AMP‑activated kinase a1 (AMPK) and downregulation of TGF‑β1. The effects of CNP on AMPK and TGF‑β1 levels were inhibited by KT5823 and pertussis toxin, inhibitors of protein kinase G (PKG) and NP receptor type C (NPR‑C), respectively. Thus, CNP can prevent Ang II‑induced dysregulation of Cx40 and Cx43 through activation of AMPK via the CNP‑PKG and CNP‑NPR‑C pathways in isolated beating rat atria. The present findings suggested that CNP may be therapeutically useful for clinical conditions involving cardiac dysregulation of Cx expression‑related diseases.