Document Detail

Arachidonic acid metabolites mediate angiotensin II-induced NADH/NADPH oxidase activity and hypertrophy in vascular smooth muscle cells.
MedLine Citation:
PMID:  11228745     Owner:  NLM     Status:  MEDLINE    
Previously, we showed that angiotensin II stimulation of the NADH/NADPH oxidase is involved in hypertrophy of cultured vascular smooth muscle cells (VSMC). Here, we examine the pathways leading to oxidase activation, and demonstrate that arachidonic acid metabolites mediate hypertrophy by activating the p22phox-based NADH/NADPH oxidase. Angiotensin II stimulates phospholipase A2, releasing arachidonic acid, which stimulates oxidase activity in vitro. When arachidonic acid metabolism is blocked with 5,8,11,14-eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA), oxidase activity decreases by 80 +/- 10%. In VSMC transfected with antisense p22phox to attenuate NADH/NADPH oxidase expression, arachidonic acid is unable to stimulate NADH/NADPH-dependent superoxide production. In these cells, or in cells in which NADH/NADPH oxidase activity is inhibited by diphenylene iodonium, angiotensin II-induced [3H]leucine incorporation is also inhibited. Attenuation of oxidase activation by inhibiting arachidonic acid metabolism with ETYA, NDGA, baicalein, or SKF-525A also inhibits angiotensin II-stimulated protein synthesis (74 +/- 2% and 34 +/- 1%, respectively). Thus, endogenous noncyclooxygenase arachidonic acid metabolites mediate angiotensin II-stimulated protein synthesis in cultured VSMC by activating the NADH/NADPH oxidase, providing mechanistic evidence for redox control of VSMC hypertrophy.
A M Zafari; M Ushio-Fukai; C A Minieri; M Akers; B Lassègue; K K Griendling
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  1     ISSN:  1523-0864     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  1999  
Date Detail:
Created Date:  2001-03-02     Completed Date:  2001-03-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  167-79     Citation Subset:  IM    
Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
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MeSH Terms
Angiotensin II / pharmacology*
Aorta, Thoracic
Arachidonic Acid / antagonists & inhibitors,  biosynthesis,  metabolism*,  physiology
Cells, Cultured
Enzyme Activation
Intracellular Fluid / metabolism
Membrane Transport Proteins*
Muscle, Smooth, Vascular / drug effects,  enzymology*,  metabolism,  pathology*
NADH, NADPH Oxidoreductases / genetics,  metabolism*
NADPH Dehydrogenase / genetics,  metabolism
NADPH Oxidase
Phospholipases A / physiology
Phospholipases A2
Phosphoproteins / genetics,  metabolism
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin / antagonists & inhibitors,  physiology
Grant Support
Reg. No./Substance:
0/Membrane Transport Proteins; 0/Phosphoproteins; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Angiotensin; 11128-99-7/Angiotensin II; 506-32-1/Arachidonic Acid; EC 1.6.-/NADH, NADPH Oxidoreductases; EC protein, human; EC Oxidase; EC Dehydrogenase; EC 3.1.1.-/Phospholipases A; EC A2

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