Document Detail


PPAR-gamma agonist rosiglitazone reverses increased cerebral venous hydraulic conductivity during hypertension.
MedLine Citation:
PMID:  19666838     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been shown to protect the cerebral vasculature, including the blood-brain barrier. In the present study, we investigated the effect of the PPAR-gamma agonist rosiglitazone on changes in venous permeability during chronic hypertension induced by nitric oxide synthase inhibition. Female Sprague-Dawley rats were either treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5 g/l in drinking water) for 5 wk (HTN; n = 8), L-NAME for 5 wk plus the PPAR-gamma agonist rosiglitazone (20 mg/kg in food) for the last 3 wk (HTN + Rosi; n = 5), L-NAME for 5 wk plus the superoxide dismutase mimetic Tempol (1 mmol/l in drinking water) for the last 3 wk (HTN + Tempol; n = 8), or were untreated controls (n = 9). Fluid filtration (J(v)/S) and hydraulic conductivity (L(p)) of cerebral veins were compared in vitro between groups after a step increase in pressure from 10 to 25 mmHg to mimic the change in hydrostatic pressure during acute hypertension. Hypertension increased J(v)/S by 2.2-fold and L(p) by 3.2-fold. Rosiglitazone treatment after 2 wk of hypertension completely reversed the increased J(v)/S and L(p) that occurred during hypertension, whereas Tempol had no effect. These results demonstrate that rosiglitazone was effective at reversing changes in venous permeability that occurred during chronic hypertension, an effect that does not appear to be related to its antioxidant properties. Our findings suggest that PPAR-gamma may be a key regulator of blood-brain barrier permeability and a potential therapeutic target during hypertension.
Authors:
Tim J M Roberts; Abbie C Chapman; Marilyn J Cipolla
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-08-07
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  297     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-25     Completed Date:  2009-10-08     Revised Date:  2011-11-24    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1347-53     Citation Subset:  IM    
Affiliation:
1Departments of Neurology, Obstetrics, Gynecology and Reproductive Sciences, and Pharmacology, University of Vermont, Burlington, Vermont 05405, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / pharmacology*
Antioxidants / pharmacology
Blood Pressure / drug effects
Brain Edema / etiology,  physiopathology,  prevention & control
Capillary Permeability / drug effects*
Cerebral Veins / drug effects*,  metabolism,  physiopathology
Cerebrovascular Circulation / drug effects*
Chronic Disease
Cyclic N-Oxides / pharmacology
Disease Models, Animal
Female
Hydrostatic Pressure
Hypertension / chemically induced,  drug therapy*,  metabolism,  physiopathology
NG-Nitroarginine Methyl Ester
PPAR gamma / agonists*
Rats
Rats, Sprague-Dawley
Spin Labels
Thiazolidinediones / pharmacology*
Time Factors
Grant Support
ID/Acronym/Agency:
NS043316/NS/NINDS NIH HHS; NS045940/NS/NINDS NIH HHS; R01 NS043316-01A2/NS/NINDS NIH HHS; R01 NS045940-05A2/NS/NINDS NIH HHS; R01 NS045940-08/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Antioxidants; 0/Cyclic N-Oxides; 0/PPAR gamma; 0/Spin Labels; 0/Thiazolidinediones; 122320-73-4/rosiglitazone; 2226-96-2/tempol; 50903-99-6/NG-Nitroarginine Methyl Ester

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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