Npr1 gene (coding for NPR-A) and Npr2 gene (coding for NPR-B) are identified as intrinsic antihypertrophic genes that opposes abnormal cardiac remodeling. However, the functional role of Nprl and Npr2 genes during cardiac hypertrophic growth is not well understood. Hence, the present investigation was aimed to study the effect of Nprl and Npr2 gene silencing, respectively on beta-AR activation induced cardiac hypertrophic growth in H9c2 cells in vitro. The control, Nprl, and Npr2 gene suppressed H9c2 cells, respectively were treated with ISO (10(-5) M) for 48 h. The mRNA and protein expression profile of NPR-A, NPR-B, PKG-I and cGMP were analyzed by qPCR, Western blotting, ELISA, and immunofluorescence methods, respectively. A marked increase in cell size (30.10 +/- 0.51 mu m vs 61.83 +/- 0.43 mu m, 2 -fold) accompanied by elevated hypertrophic marker genes (alpha-sk and beta-MHC 3-fold, respectively) expression was observed in Nprl gene suppressed H9c2 cells as compared with control cells. In contrast, the Npr2 gene suppression in H9c2 cells neither altered the cell size nor the level of hypertrophic marker genes expression. Upon exposure to Isoproterenol, the Nprl suppressed H9c2 cells exhibited further increase in cell size (1.5 fold), whereas, no significant increase in cell size or marker genes expression was noticed in Npr2 suppressed cells. Moreover, the intracellular cGMP level was down -regulated by 2 -fold in Nprl suppressed cells, while, no significant change was observed in Npr2 suppressed cells. Together, these results suggest that Nprl, not Npr2 gene function is positively associated with the initiation of cardiac fetal gene program and development of cardiac hypertrophic growth. (C) 2017 Elsevier Inc. All rights reserved.