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 alpha1-adrenergic receptors (alpha1-AR). Reactive oxygen species (ROS) can act as signaling molecules for cell growth. Accordingly, we tested the hypothesis that ROS mediate alpha1-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. alpha1-AR stimulation with NE (1 microM) in the presence of propranolol (2 microM) for 48-96 h caused a hypertrophic growth phenotype characterized by a 36+/-3% increase in 3H-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 alpha1-AR-selective antagonist prazosin (100 n M) or the SOD-mimetics MnTMPyP (50 microM) and Euk-8 (100 microM). MnTMPyP had no effect on alpha1-AR-stimulated 3H-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 alpha1-AR-stimulation in ARVM.
Amin
J K
JK
The Cardiovascular Section, Boston Medical Center, Boston, MA, USA.
Xiao
L
L
Pimental
D R
DR
Pagano
P J
PJ
Singh
K
K
Sawyer
D B
DB
Colucci
W S
WS
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005029:Ethylenediamines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy; D007295:Inositol Phosphates / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009638:Norepinephrine / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics
D000199:Actins; D005029:Ethylenediamines; D007295:Inositol Phosphates; D009942:Organometallic Compounds; D011166:Porphyrins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018340:Receptors, Adrenergic, alpha-1; C021096:tetra(4-N-methylpyridyl)porphine; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); D009320:Atrial Natriuretic Factor; D013482:Superoxide Dismutase; D009638:Norepinephrine; D011224:Prazosin