Document Detail

NADPH oxidase activity and function are profoundly greater in cerebral versus systemic arteries.
MedLine Citation:
PMID:  16210546     Owner:  NLM     Status:  MEDLINE    
Recent studies suggest that the superoxide generating enzyme NADPH oxidase may play a functional role in regulating cerebral vascular tone. We tested whether the activity, function, and expression of NADPH oxidase differs between rat cerebral and systemic arteries. Superoxide production by basilar (BA), middle cerebral (MCA), carotid (CA), renal (RA), and mesenteric (MA) arteries and aorta (AO) was measured using lucigenin-enhanced chemiluminescence. Superoxide production from NADPH oxidase was localized and semiquantified using dihydroethidium. Vascular functional responses were assessed in a myograph or organ bath. Vascular Nox4 protein expression was measured using Western blotting. Superoxide production (basal or in response to NADPH or angiotensin II) in the intracranial arteries, BA, and MCA was 10- to 100-fold greater than in AO, CA, RA, or MA. Similar results were found using either intact vessels or arterial homogenates, and were associated with 10-fold greater expression of Nox4 in the BA versus AO, CA, and MA. Superoxide production was attenuated by the NADPH oxidase inhibitors, diphenyleneiodonium, apocynin, and gp91ds-tat. NADPH and H2O2 were strong relaxing stimuli in the BA, where the H2O2 scavenger catalase, as well as apocynin, attenuated these relaxations and also augmented contractions to angiotensin II. NADPH oxidase activity is markedly higher in intracranial versus systemic arteries, in association with higher Nox4 expression. In cerebral arteries, endogenous H2O2 derived from NADPH oxidase activation appears to cause relaxation and is able to offset angiotensin II-induced constriction. These data are consistent with the concept that NADPH oxidase-derived reactive oxygen species modulate cerebral vascular tone under physiological conditions.
Alyson A Miller; Grant R Drummond; Harald H H W Schmidt; Christopher G Sobey
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-06
Journal Detail:
Title:  Circulation research     Volume:  97     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-14     Completed Date:  2005-12-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1055-62     Citation Subset:  IM    
Department of Pharmacology, University of Melbourne, Parkville, Victoria 3010, Australia.
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MeSH Terms
Angiotensin II / pharmacology
Arteries / enzymology*
Cerebral Arteries / enzymology*
Hydrogen Peroxide / pharmacology
NADP / pharmacology
NADPH Oxidase / blood,  genetics,  physiology*
Nitroprusside / pharmacology
RNA, Messenger / analysis
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Superoxides / metabolism
Vasoconstriction / drug effects
Vasodilation / drug effects
Reg. No./Substance:
0/RNA, Messenger; 0/Reactive Oxygen Species; 11062-77-4/Superoxides; 11128-99-7/Angiotensin II; 15078-28-1/Nitroprusside; 53-59-8/NADP; 7722-84-1/Hydrogen Peroxide; EC 1.6.-/Nox4 protein, rat; EC Oxidase

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