Differential expression and regulation of anti-hypertrophic genes Npr1 and Npr2 during β-adrenergic receptor activation-induced hypertrophic growth in rats.
We sought to determine the effect of chronic activation of β-adrenergic receptor (β-AR) on the left ventricular (LV) expression profile of Npr1 and Npr2 (coding for NPR-A and NPR-B, respectively) genes, and the functional activity of these receptors in adult Wistar rat hearts. The Npr1 gene expression was markedly reduced (3.5-fold), while the Npr2 gene expression was up regulated (4-fold) in Isoproterenol (ISO)-treated heart as compared with controls. A gradual reduction in NPR-A protein (3-fold), cGMP levels (75%) and a steady increased expression of NPR-B protein (4-fold), were noticed in ISO hearts. 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. Atenolol treatment normalized the altered expression of Npr1 and Npr2 genes. In conclusion, the chronic β-AR activation differentially regulates Npr1 and Npr2 genes in the heart. Npr1 down regulation is positively associated with the development of left ventricular hypertrophy (LVH) in ISO rats.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
Senthamizharasi
S
Manivasagam
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
Vimala
V
Subramanian
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
Anusha
A
Tumala
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India. Electronic address: vellaie@gmail.com.
Elangovan
E
Vellaichamy
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006152:Cyclic GMP / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D006162:Guanylate Cyclase / Q000235:genetics; D006321:Heart / Q000502:physiology; D006984:Hypertrophy / Q000235:genetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D000099242:Atrial Natriuretic Factor Receptor B
D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D006162:Guanylate Cyclase; D011943:Receptors, Adrenergic, beta; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B; C091715:atrial natriuretic factor receptor A
Cardiac hypertrophy; Natriuretic peptide receptors; Natriuretic peptides; cGMP; β-adrenergic signaling