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

OBJECTIVES The study investigated whether β-adrenoceptor antagonists augment the hypertrophic response of cardiomyocytes evoked by norepinephrine. BACKGROUND In adult ventricular cardiomyocytes, stimulation of α- but not β-adrenoceptors induces myocardial hypertrophy. Natural catecholamines, like norepinephrine, stimulate simultaneously α- and β-adrenoceptors. We investigated whether β-adrenoceptor stimulation interferes with the hypertrophic response caused by α-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 14C-uridine incorporation and RNA mass, and increases in cell shape. RESULTS Norepinephrine (0.01 to 10 μmol/liter) increased concentration-dependent phenylalanine incorporation; pEC50 value was 5.9 ± 0.1 (n = 8). The α1-adrenoceptor antagonist prazosin (0.1 μmol/liter) suppressed norepinephrine-induced increase in rate of protein synthesis. Conversely, propranolol (1 μmol/liter) and the β1-adrenoceptor selective antagonists CPG 20712A (300 nmol/liter) or atenolol (1 μmol/liter) augmented increases in phenylalanine incorporation caused by norepinephrine. Addition of the β2-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 β1-adrenoceptors increased the amount of protein kinase C-α and -δ isoforms translocated into the particulate fraction. The effect of pharmacological inhibition of β1-adrenoceptors could be mimicked by Rp-cAMPS (adenosine-3′, 5′-cyclic phosphorothiolate-Rp). The inhibitory effect of β1-adrenoceptor stimulation on the α-adrenoceptor-mediated effect persisted in cardiomyocytes isolated from hypertrophic hearts of rats submitted to aortic banding. CONCLUSIONS In isolated ventricular cardiomyocytes from rats, β1-adrenoceptor stimulation attenuates the hypertrophic response evoked by α1-adrenoceptor stimulation.