INFLUENCE OF PH(I) AND CREATINE-PHOSPHATE ON ALPHA-ADRENOCEPTOR-MEDIATED CARDIAC-HYPERTROPHY

Stimulation of alpha-adrenoceptors on ventricular cardiomyocytes isola ted from adult rat hearts leads to cellular alkalization, increases of creatine phosphate concentration, RNA mass, and protein synthesis. Th is study investigated whether the increase of creatine phosphate conce ntrations is causally linked to the hypertrophic response of cardiomyo cytes under alpha-adrenoceptor stimulation. Cellular alkalization achi eved with phenylephrine (10 mu M), an alpha-adrenoceptor agonist, was abolished in the presence of the sodium-proton-exchange (NHE)-inhibito r HOE 694 (1 mu M). HOE 694 inhibited also the alpha-adrenoceptor-medi ated increase in cellular creatine phosphate and the increase in cellu lar RNA mass. The phenylephrine-induced stimulation of protein synthes is (determined by incorporation of C-14-phenylalanine) was reduced by one-third when HOE 694 was present. beta-Guanidinopropionic acid was a dded to cardiomyocytes to reduce cellular creatine phosphate concentra tions. In these cultures, alpha-adrenoceptor stimulation activated NHE , but creatine phosphate concentrations were not increased. Protein sy nthesis was augmented to the same extent as in control cultures, but t otal RNA mass did not increase. From these results we conclude that al pha-adrenoceptor stimulation causes the increase in protein synthesis via activation of NHE, but independent of the concomitant increase in creatine phosphate contents. The effect of alpha-adrenoceptor stimulat ion on total RNA mass (translational capacity) is also caused by NHE a ctivation, but depends on the changes in creatine phosphate contents a s well. (C) 1998 Academic Press Limited.