Influence of pHiand Creatine Phosphate on α-Adrenoceptor-mediated Cardiac Hypertrophy

Stimulation ofα-adrenoceptors on ventricular cardiomyocytes isolated from adult rat hearts leads to cellular alkalization, increases of creatine phosphate concentration, RNA mass, and protein synthesis. This study investigated whether the increase of creatine phosphate concentrations is causally linked to the hypertrophic response of cardiomyocytes underα-adrenoceptor stimulation. Cellular alkalization achieved with phenylephrine (10μ ), anα-adrenoceptor agonist, was abolished in the presence of the sodium–proton-exchange (NHE)-inhibitor HOE 694 (1μ ). HOE 694 inhibited also theα-adrenoceptor-mediated increase in cellular creatine phosphate and the increase in cellular RNA mass. The phenylephrine-induced stimulation of protein synthesis (determined by incorporation of14C-phenylalanine) was reduced by one-third when HOE 694 was present.β-Guanidinopropionic acid was added to cardiomyocytes to reduce cellular creatine phosphate concentrations. In these cultures,α-adrenoceptor stimulation activated NHE, but creatine phosphate concentrations were not increased. Protein synthesis was augmented to the same extent as in control cultures, but total RNA mass did not increase. From these results we conclude thatα-adrenoceptor stimulation causes the increase in protein synthesis via activation of NHE, but independent of the concomitant increase in creatine phosphate contents. The effect ofα-adrenoceptor stimulation on total RNA mass (translational capacity) is also caused by NHE activation, but depends on the changes in creatine phosphate contents as well.