Document Detail


PPAR{gamma} activation prevents hypertensive remodeling of cerebral arteries and improves vascular function in female rats.
MedLine Citation:
PMID:  20395611     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated transcription factor expressed in vascular cells, is protective of the vasculature. We hypothesized that activation of PPARgamma could prevent hypertensive remodeling of cerebral arteries and improve vascular function.
METHODS: Ten female Sprague-Dawley rats were treated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) for 5 weeks, 8 were treated with l-NAME plus the PPARgamma activator rosiglitazone, and 8 received no treatment and served as controls. Blood pressure, myogenic activity, passive diameters and wall thickness of cerebral arteries, and brain capillary density were compared between the groups.
RESULTS: Treatment with l-NAME caused an increase in arterial blood pressure that was sustained with rosiglitazone treatment. l-NAME also caused inward hypertrophic remodeling and enhanced myogenic reactivity of cerebral arteries that was reversed by rosiglitazone. In addition, l-NAME hypertension caused rarefaction of brain capillaries by approximately 12%, whereas treatment with rosiglitazone increased capillary density by approximately 20%.
CONCLUSIONS: PPARgamma activation may be an effective and clinically relevant way to prevent hypertensive remodeling of cerebral arteries and capillary rarefaction as well as improving vascular function without affecting blood pressure.
Authors:
Marilyn J Cipolla; Nicole Bishop; R Saman Vinke; Julie A Godfrey
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-04-15
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  41     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-06-11     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1266-70     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Brain / blood supply,  physiopathology
Capillaries / physiopathology
Cerebral Arteries / metabolism,  physiopathology*
Enzyme Inhibitors / pharmacology
Female
Hypertension / chemically induced,  metabolism,  physiopathology*
Hypoglycemic Agents / pharmacology*
NG-Nitroarginine Methyl Ester / pharmacology
PPAR gamma / agonists*,  metabolism
Rats
Rats, Sprague-Dawley
Thiazolidinediones / pharmacology*
Grant Support
ID/Acronym/Agency:
NS043316/NS/NINDS NIH HHS; NS045940/NS/NINDS NIH HHS; R01 NS043316/NS/NINDS NIH HHS; R01 NS043316-05/NS/NINDS NIH HHS; R01 NS045940/NS/NINDS NIH HHS; R01 NS045940-06/NS/NINDS NIH HHS; R01 NS045940-07/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 122320-73-4/rosiglitazone; V55S2QJN2X/NG-Nitroarginine Methyl Ester
Comments/Corrections

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