Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes

Norepinephrine (NE) causes hypertrophic growth of cardiac myocytes via stimulation of alpha(1)-adrenergic receptors (alpha (1)-AR). Reactive oxygen species (ROS) can act as signaling molecules for cell growth. Accordingly, we tested the hypothesis that ROS mediate alpha (1)-AR-stimulated hypertrophic growth in adult rat ventricular myocytes (ARVM). NE increased the level of intracellular ROS as assessed by lucigenin chemiluminescence or cytochrome c reduction, and this effect was prevented by the superoxide dismutase (SOD)-mimetic MnTMPyP. NE also caused the induction of MnSOD mRNA. alpha (1)-AR stimulation with NE (1 muM) in the presence of propranolol (2 muM) for 48-96 h caused a hypertrophic growth phenotype characterized by a 36 +/- 3% increase in H-3-leucine incorporation, a 49 +/- 14% increase in protein accumulation, a six-fold induction of atrial natriuretic peptide mRNA, actin filament reorganization, and the induction of MnSOD mRNA. These responses were all prevented by pretreatment with the alpha (1)-AR-selective antagonist prazosin (100 nM) or the SOD-mimetics MnTMPyP (50 muM) and Euk-8 (100 muM). MnTMPyP had no effect on alpha (1)-AR-stimulated H-3-inositol phosphate turnover or the hypertrophic phenotype caused by the protein kinase C activator phorbol-12-myristate-13-acetate. Thus, ROS play a critical role in mediating the hypertrophic growth response to alpha (1)-AR-stimulation in ARVM. (C) 2000 Academic Press.