HYPERTROPHIC RESPONSIVENESS TO BETA(2)-ADRENOCEPTOR STIMULATION ON ADULT VENTRICULAR CARDIOMYOCYTES

The aim of the present study was to characterize the receptor subtype and the second messenger involved in the newly discovered hypertrophic effect of beta-adrenoceptor stimulation in cultures of adult ventricu lar cardiomyocytes. Cardiomyocytes isolated from adult rats and cultur ed for 6 days in presence of 20% fetal calf serum (FCS) were used as e xperimental model. Hypertrophic responsiveness of cardiomyocytes was c haracterized by rate of protein synthesis, increase in protein mass, a nd increase in RNA content. The hypertrophic effect of the non-specifi c beta-adrenoceptor agonist isoprenaline was abolished in presence of a specific beta(2)-adrenoceptor antagonist (ICI 118,551), could be mim icked by use of a beta(2)-adrenoceptor agonist (procaterol) or direct stimulation of adenylate cyclase (forskolin) or addition of a cell-per meable analogue of cAMP (dibuytyrylcyclo-AMP). In presence of Rp-cAMPS , an inhibitor of protein kinase A, the hypertrophic effect of isopren aline was abolished. The results indicate that the hypertrophic effect of beta-adrenoceptor stimulation is due to stimulation of beta(2)-adr enoceptors and activation of adenylate cyclase and protein kinase A.