Differential expression and regulation of anti- hypertrophic genes Npr1 and Npr2 during β- adrenergic receptor activation- induced hypertrophic growth in rats

posted Jan 26, 2017, 1:28 AM by sourav ghosh
Elangovan Vellaichamy
Peptide Research and Molecular Cardiology Unit, Department of Biochemistry, University of Madras, Guindy campus, Chennai, India

The natriuretic peptides (NPs) family is consists of three important peptides namely atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP).ANP and BNP elicits its physiological action by specific binding to Natriureitc Peptide Receptor-A/Guanylyl cyclase-A (NPR-A/GC-A), while CNP binds to Natriureitc Peptide Receptor-B/ Guanylyl cyclase-B (NPR-B/ GC-B).Recent studies have suggested that ANP/NPR-A/GC-Aand CNP/NPR-B/GC-B system are present in the heart as a negative regulatory mechanisms to antagonize the cardiac growth response to hypertrophic stimuli.Since NPs has the potential to inhibit cardiac hypertrophic growth via NPR-A/NPR-B receptors, understanding the regulation and expression of NPR-A and –Bin the heart during the diseased conditions will help to target specific NPRs subtype to increase the physiological actions of NPs, and thus may be useful as therapy for cardiac hypertrophy and heart failure. In this context, we have studiedleft ventricular (LV) expression ofNPR-A (coded by Npr1) and NPR-B (coded by Npr2), and the functional activity of these receptors during β-adrenergic receptor (β-AR) activation induced hypertrophic growth in experimental rats. The NPR-A expression was markedly reduced (3.5-fold), while the NPR-B expression was up regulated (4-fold) in Isoproterenol (ISO)-treated heart as compared with controls.. Further, in-vitro membranes assay shows that NPR-A dependent guanylyl cyclase (GC) activity was down-regulated (2-fold), whereas NPR-B dependent GC activity was increased (5-fold) in ISO treated hearts. β –blocker (atenolol) treatment normalized the altered expression ofNPR-A and –B proteins. Our results suggests that the chronic β-AR activation differentially regulates NPR-A/GC-A and NPR-B/GC-Bin the heart. The signifcance of this finding will be discussed during the presentation.