Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha1 adrenergic response

Abstract

We have shown recently that norepinephrine stimulates muscle cell hypertrophy in primary cultures from the neonatal rat ventricle and that this stimulation is not blocked by the beta adrenergic antagonist propranolol. The present study was done to define the adrenergic specificity of the myocyte hypertrophic response to norepinephrine. 90% pure, single-cell cultures of nongrowing myocytes were maintained in serum-free medium 199 with transferrin and insulin. Myocyte size was quantitated 48 h after addition of adrenergic agents, by measuring cell volume, cell surface area, and cell protein. L-norepinephrine increased myocyte size to a maximum 150% of control; half-maximum effect was obtained at a concentration of 0.2 μM. This increase in cell size was inhibited by the nonselective alpha adrenergic antagonist phentolamine and by the alpha1 adrenergic antagonists prazosin and terazosin; it was not inhibited by propranolol or by the alpha2 adrenergic antagonist yohimbine. The beta adrenergic agonist isoproterenol did not increase cell size. Thus, norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha1 adrenergic response. We have shown recently the myocyte (MC) hypertrophy and its regulation can be studied in primary cultures obtained from neonatal rat hearts. Norepinephrine (NE) stimulates MC hypertrophy, both in serum-supplemented cultures with enlarging MCs and in serum-free cultures. MCs in serum-free cultures beat rarely and do not enlarge, but they are viable and responsive to growth stimulation by serum and by NE. The hypertrophic effect of NE is not due to a sustained chronotropic action and is not blocked by the beta adrenergic antagonist propranolol. In this study, using serum-free cultures and several adrenergic antagonists, we show that the stimulation of MC hypertrophy by NE is an alpha1 adrenergic response.