Role of beta 1- and beta 2-adrenoceptors in hypertrophic and apoptotic effects of noradrenaline and adrenaline in adult rat ventricular cardiomyocytes.

Abstract

In adult rat ventricular cardiomyocytes alpha1-adrenoceptor (AR) stimulation causes increases in protein synthesis. On the other hand beta1-AR stimulation inhibits protein synthesis, and evokes apoptotic cell death. We studied, in adult rat ventricular cardiomyocytes, effects of noradrenaline (NA), adrenaline (ADR) and phenylephrine (PE) on protein synthesis (assessed by [3H]-phenylalanine incorporation into the cardiomyocytes) in relation to effects on early apoptosis (measured by Annexin V/propidium iodide staining). PE (10(-9)-10(-5) M) induced protein synthesis was not affected by the beta1-AR blocker CGP 20712A (CGP, 300 nM) or beta2-AR blocker ICI 118,551 (ICI, 55 nM). ADR (10(-9)-10(-5) M) induced protein synthesis was enhanced by CGP and decreased by ICI. Pretreatment of the cardiomyocytes with pertussis toxin (PTX) decreased NA- and ADR- induced protein synthesis, but did not affect PE-effects. NA (10(-5) M) and ADR (10(-5) M) caused a significant increase in the number of apoptotic cells; these effects were enhanced by PTX-treatment, abolished by CGP, but not significantly affected by ICI. Furthermore, there was a significant negative correlation between catecholamine-evoked apoptosis and catecholamine-induced hypertrophic effects. We conclude that, in ventricular cardiomyocytes of adult rats, growth-promoting effects of NA and ADR are composed of alpha1A-AR mediated increase in protein synthesis and beta1-AR mediated apoptosis that counteracts increases in protein synthesis. The role of beta2-adrenoceptor appears to be a balance of antiapoptotic effects via a PTX-sensitive pathway and proapoptotic effects via a GS-adenylyl cyclase pathway.