Effect And Mechanism Of C-type Natriuretic Peptide Against Ang ?-induced Atrial Connexin Dysregulation In Beating Rat Atria

Aim:C-type natriuretic peptide(CNP),from a family of natriuretic peptides,was shown to have anti-hypertrophic and anti-fibrotic effects in cardiomyocytes.However,the role of CNP on atrial connexin dysregulation is not clear.The present study,therefore,to investigated effect of CNP on angiotensin ?(Ang ?)-induced atrial connexin dysregulation in isolated perfused beating rat left atria.Methods:Isolated perfused beating rat atrial model was used and protein levels were determined by Western blot.Results:Excessive Ang II significantly upregulated nuclear factor-KB,activator protein-1,transforming growth factor-beta 1(TGF-?1),collagen I and matrix matalloproteinase 2,ultimately leading to atrial fibrosis and dowregulation of connexin 40(Cx40)and Cx43 expression.Ang ?-incued atrial nuclear factors,TGF-?1,changes of extracellular matrix and Cxs dysregulation were dramatically abolished by CNP via activation of AMP-activated protein kinase(AMPK).Moreover,KT5823(an inhibitor of protein kinase G,PKG)and pertussis toxin(an inhibitor of natriuretic peptide type C receptor,NPR-C)may obviously blocked the role of CNP on Ang ?-incued atrial fibrosis and dysregulation of Cx40 as well as Cx43.Conclusion:CNP prevents Ang II-induced Cx40 and Cx43 dysregulation by activation of NPR-B-AMPK and NPR-C-AMPK signaling.The results indicate that CNP-NPR-AMPK signaling pathway may used for Cx40 and Cx43 dysregulated cardiac diseases therapy.