The study addressed the question of why in adult ventricular rat cardiomyocytes ERK activation is required for the hypertrophic stimulation caused by angiotensin II but not in the case of alpha-adrenoceptor stimulation. We therefore compared in the same culture system the intracellular signaling steps that are involved in inducing the hypertrophic growth evoked by stimulating either of these two receptors. alpha-Adrenoceptor stimulation strongly increased protein synthesis ([14C]phenylalanine incorporation) up to 53% in a PKC- and p70s6k-dependent, but ERK-independent way. In contrast, angiotensin II increased protein synthesis less efficiently (by 23%), in a PKC-, p70s6k-, but ERK-dependent way. The kinetics of activation for ERK were different for the two hypertrophic stimuli: alpha-adrenoceptor stimulation caused a rapid and transient activation, but angiotensin II caused a rapid and sustained activation. In contrast to alpha-adrenoceptor stimulation, angiotensin II activated calcium-independent PKC isoforms but not calcium-dependent PKC isoforms. In conclusion, ERK activation by angiotensin II is sustained and leads to an increase in protein synthesis on adult ventricular cardiomyocytes, but ERK activation by alpha-adrenoceptor stimulation is transient and not involved in hypertrophic growth responsiveness. The ERK-dependent pathway seems to be less efficient than ERK-independent pathways. The difference in the hypertrophic responsiveness of cardiomyocytes exposed to either of the two stimuli may be explained by the activation of different PKC isoform types.

Our data indicate that several aspects of myocardial hypertrophy are accelerated by smoking.