Reactive Oxygen Species Mediate Alpha-adrenergic Receptor-stimulated Hypertrophy in Adult Rat Ventricular Myocytes

• Published in: Journal of molecular and cellular cardiology 2001-01, Vol.33 (1), p.131-139
• Main Authors: Amin, Jay K, Xiao, Lei, Pimental, David R, Pagano, Patrick J, Singh, Krishna, Sawyer, Douglas B, Colucci, Wilson S
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - ultrastructure; Actins - metabolism; Animals; Atrial Natriuretic Factor - biosynthesis; Atrial Natriuretic Factor - genetics; Cell Division - drug effects; Enzyme Induction - drug effects; Ethylenediamines - pharmacology; Gene Expression Regulation - drug effects; Heart - drug effects; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heart Ventricles - pathology; Hypertrophy; Inositol Phosphates - metabolism; Myocardium - metabolism; Myocardium - pathology; Myocyte; Norepinephrine - pharmacology; Organometallic Compounds - pharmacology; Porphyrins - pharmacology; Prazosin - pharmacology; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Adrenergic, alpha-1 - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal Transduction; Superoxide dismutase; Superoxide Dismutase - biosynthesis; Superoxide Dismutase - genetics; α1-adrenergic receptor
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.2000.1285

Norepinephrine (NE) causes hypertrophic growth of cardiac myocytes via stimulation of alpha1-adrenergic receptors (α1-AR). Reactive oxygen species (ROS) can act as signaling molecules for cell growth. Accordingly, we tested the hypothesis that ROS mediate α1-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. α1-AR stimulation with NE (1 μM) in the presence of propranolol (2 μM) for 48–96 h caused a hypertrophic growth phenotype characterized by a 36±3% increase in3H-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 α1-AR-selective antagonist prazosin (100 nM ) or the SOD-mimetics MnTMPyP (50 μM) and Euk-8 (100 μM). MnTMPyP had no effect on α1-AR-stimulated3H-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 α1-AR-stimulation in ARVM.