Amplification of angiotensin II signaling in cardiac myocytes by adenovirus-mediated overexpression of the AT1 receptor

Low levels of AT(1) receptor can make studying the growth related signal transduction events mediated by this angiotensin II receptor in cardiac myocytes technically difficult, The purpose of the present study was to establish whether an adenovirus expression system could be used to increase the number of plasma membrane AT(1) receptors in neonatal rat ventricular myocytes, thereby amplifying the signaling pathways activated by this receptor. Cardiac myocytes infected with adenovirus expressing the AT(1) receptor exhibited increased ligand binding. The overexpressed receptor appeared to function like the endogenous receptor, in regard to agonist-induced internalization, as well as coupling to MAPK activation and protein tyrosine phosphorylation events. In addition, adenovirus-mediated overexpression of the AT(1) receptor resulted in the amplification of angiotensin II intracellular signaling. In conclusion, adenovirus-mediated overexpression of angiotensin II receptors appears to be a useful strategy for studying the signal transduction events activated by this hormone in cardiac myocytes and for unraveling the molecular means by which this receptor type couples to a hypertrophic pattern of growth and gene expression.