|Cyclooxygenase-2-dependent superoxide generation contributes to age-dependent impairment of G protein-mediated cerebrovasodilation.|
|PMID: 12766646 Owner: NLM Status: MEDLINE|
|BACKGROUND: Previous studies have observed that activation of cyclooxygenase-2 contributes to generation of superoxide anion after fluid percussion brain injury (FPI). This study was designed to characterize the effects of FPI on the vascular activity of two activators of a pertussis toxin-sensitive G protein, mastoparan and mastoparan-7, and the role of cyclooxygenase-2-dependent superoxide anion generation in such effects as a function of age. METHODS: Lateral FPI was induced in anesthetized newborn (1-5-day-old) and juvenile (3-4-week-old) pigs equipped with a closed cranial window. RESULTS: Mastoparan (10(-8), 10(-6) M) elicited pial artery dilation that was blunted more in newborn versus juvenile pigs (9 +/- 1 and 16 +/- 1 vs. 3 +/- 1 and 5 +/- 1%, newborn; 9 +/- 1 and 15 +/- 1 vs. 6 +/- 1 and 9 +/- 1%, juveniles). Similar results were observed for mastoparan-7 but the inactive analog mastoparan-17 had no effect on pial artery diameter. Indomethacin (a cyclooxygenase-1 and cyclooxygenase-2 inhibitor), NS398 (a cyclooxygenase-2 inhibitor), and polyethylene glycol superoxide dismutase and catalase (free radical scavengers) partially restored impaired mastoparan dilation after FPI in the newborn in a roughly equivalent manner but not in the juvenile (3 +/- 1 and 5 +/- 1 vs. 8 +/- 1 and 13 +/- 1% newborn, 6 +/- 1 and 9 +/- 1 vs. 7 +/- 1 and 10 +/- 1% juvenile for NS398 pretreatment). CONCLUSIONS: These data show that G protein activation elicits cerebrovasodilation that is blunted following FPI in an age-dependent manner, and suggest that cyclooxygenase-2-dependent superoxide anion generation contributes to G protein activation-induced dilator impairment after the insult in an age-dependent manner.|
|William M Armstead|
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|Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.|
|Title: Anesthesiology Volume: 98 ISSN: 0003-3022 ISO Abbreviation: Anesthesiology Publication Date: 2003 Jun|
|Created Date: 2003-05-26 Completed Date: 2003-06-24 Revised Date: 2006-11-15|
Medline Journal Info:
|Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States|
|Languages: eng Pagination: 1378-83 Citation Subset: AIM; IM|
|Department of Anesthesia, University of Pennsylvania, Philadelphia, 19104, USA. firstname.lastname@example.org|
|APA/MLA Format Download EndNote Download BibTex|
Arteries / physiology
Blood Chemical Analysis
Brain Injuries / physiopathology
Catalase / pharmacology
Cerebrovascular Circulation / physiology*
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / pharmacology
Free Radical Scavengers / pharmacology
GTP-Binding Proteins / physiology*
Indomethacin / pharmacology
Isoenzymes / metabolism*
Nitrobenzenes / pharmacology
Pertussis Toxin / pharmacology
Prostaglandin-Endoperoxide Synthases / metabolism*
Sulfonamides / pharmacology
Superoxide Dismutase / pharmacology
Superoxides / metabolism*
Vasodilation / physiology*
Wasp Venoms / pharmacology
|0/Cyclooxygenase 2 Inhibitors; 0/Cyclooxygenase Inhibitors; 0/Free Radical Scavengers; 0/Isoenzymes; 0/Nitrobenzenes; 0/Peptides; 0/Sulfonamides; 0/Wasp Venoms; 11062-77-4/Superoxides; 123653-11-2/N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; 53-86-1/Indomethacin; 72093-21-1/mastoparan; EC 184.108.40.206/Catalase; EC 220.127.116.11/Cyclooxygenase 2; EC 18.104.22.168/Prostaglandin-Endoperoxide Synthases; EC 22.214.171.124/Superoxide Dismutase; EC 126.96.36.199/Pertussis Toxin; EC 3.6.1.-/GTP-Binding Proteins|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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