Beta-adrenoceptor stimulation attenuates the hypertrophic effect of alpha-adrenoceptor stimulation in adult rat ventricular cardiomyocytes

OBJECTIVES The study investigated whether beta -adrenoceptor antagonists augment the hypertrophic response of cardiomyocytes evoked by norepinephrine. BACKGROUND In adult ventricular cardiomyocytes, stimulation of alpha- but not beta -adrenoceptors induces myocardial hypertrophy. Natural catecholamines, like norepinephrine, stimulate simultaneously alpha- and beta -adrenoceptors. We investigated whether beta -adrenoceptor stimulation interferes with the hypertrophic response caused by alpha -adrenoceptor stimulation. METHODS Adult ventricular cardiomyocytes isolated from rats were used as an experimental model. Hypertrophic parameters under investigation were stimulation of phenylalanine incorporation and protein mass, stimulation of C-14-uridine incorporation and RNA mass, and increases in cell shape. RESULTS Norepinephrine (0.01 to 10 mu mol/liter) increased concentration-dependent phenylalanine incorporation; pEC(50) value was 5.9 +/- 0.1 (n = 8). The alpha (1)-adrenoceptor antagonist prazosin (0.1 mu mol/liter) suppressed norepinephrine-induced increase in rate of protein synthesis. Conversely, propranolol(1 mu mol/liter) and the beta (1)-adrenoceptor selective antagonists CPG 20712A (300 nmol/liter) or atenolol (1 mu mol/liter) augmented increases in phenylalanine incorporation caused by norepinephrine. Addition of the beta (2)-adrenoceptor antagonist ICI 118,551 (55 nmol/liter) did not influence the hypertrophic effect of norepinephrine. Atenolol augmented the norepinephrine-induced increases of all hypertrophic parameters investigated (i.e., protein mass, uridine incorporation, RNA mass, cell volume, and cross-sectional area). In the presence of norepinephrine, inhibition of beta (1)-adrenoceptors increased the amount of protein kinase C-alpha and -delta isoforms translocated into the particulate fraction. The effect of pharmacological inhibition of beta (1)-adrenoceptors could be mimicked by Rp-cAMPS (adenosine-3', 5'-cyclic phosphorothiolate-Rp). The inhibitory effect of beta (1)-adrenoceptor stimulation on the alpha -adrenoceptor-mediated effect persisted in cardiomyocytes isolated from hypertrophic hearts of rats submitted to aortic banding. CONCLUSIONS In isolated ventricular cardiomyocytes from rats, beta (1)-adrenoceptor stimulation attenuates the hypertrophic response evoked by alpha (1)-adrenoceptor stimulation. (J Am Cell Cardiol 2001;37: 300-7) (C) 2001 by the American College of Cardiology.