G_q- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following α₁-Adrenergic stimulation

α₁-Adrenergic agonists activate a hypertrophie response in cultured neonatal ventricular myocytes, which include an increase in cell size, organization of contractile proteins into sarcomeric units, and the induction of the atrial natriuretic factor (ANF) gene. Previous findings have supported a role for ras in this signaling pathway. Utilizing microinjection techniques to deliver affinity-purified neutralizing antibodies to Gα_q,11 into cultured ventricular myocytes, the current studies demonstrate a functional requirement for the heterotrimeric G protein, G_q, in the α₁-adrenergic induction of the ANF gene, changes in cell size, organization of myofilaments, and phosphoinositide hydrolysis. Expression of a constitutively active mutant of Gα_q leads to the expression of ANF protein in these cells. Taken together, these data suggest that G_q-dependent pathways are necessary and sufficient to activate defined features of the hypertrophic response. In attempts to further delineate the relative roles of ras and G_q in this pathway, we found that Gα_q is required for α₁-adrenergic phosphoinositide hydrolysis, though ras does not appear to be necessary for this response. In addition, we coexpressed an inhibitory ras mutant, along with the constitutively active Gα_q. Expression of ANF protein stimulated by the Gα_q mutant was not inhibited. Thus, both ras- and G_q-dependent pathways are necessary to fully transduce defined features of α₁-adrenergic-stimulated hypertrophy of neonatal cardiac ventricular myocytes, but activated G_q may be able to induce ANF expression independent of inhibitory ras.