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

https://doi.org/10.1006/jmcc.2000.1285Get rights and content

Abstract

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.

References (41)

  • A Clerk et al.

    Stimulation of ««stress-regulated»» mitogen-activated protein kinases (stress-activated protein kinases/c-Jun N-terminal kinases and p38-mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses

    J Biol Chem

    (1998)
  • R Gopalakrishna et al.

    Selenocompounds induce a redox modulation of protein kinase C in the cell, compartmentally independent from cytosolic glutathione: its role in inhibition of tumor promotion

    Arch Biochem Biophys

    (1997)
  • P Simpson

    Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response

    J Clin Invest

    (1983)
  • CS Long et al.

    Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells

    J Clin Invest

    (1989)
  • KD Schluter et al.

    Regulation of growth in the adult cardiomyocytes

    FASEB J

    (1999)
  • K Irani et al.

    Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts

    Science

    (1997)
  • KK Griendling et al.

    Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells

    Circ Res

    (1994)
  • K Nakamura et al.

    Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-alpha and angiotensin II

    Circulation

    (1998)
  • DA Siwik et al.

    Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro

    Circ Res

    (1999)
  • C Communal et al.

    Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the β -adrenergic pathway

    Circulation

    (1998)
  • Cited by (0)

    Please address all correspondence to: Wilson S. Colucci, M.DCardiovascular Section, Boston University Medical Center, 88 East Newton Street, Boston, MA 02118, USA. Fax: 617-638-8712. E-mail: [email protected]

    View full text