HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/H1347    most recent 00630.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Roberts, T. J. M. Articles by Cipolla, M. J. PubMed PubMed Citation Articles by Roberts, T. J. M. Articles by Cipolla, M. J.

PPAR- agonist rosiglitazone reverses increased cerebral venous hydraulic conductivity during hypertension

¹Departments of Neurology, Obstetrics, Gynecology and Reproductive Sciences, and Pharmacology, University of Vermont, Burlington, Vermont; and ²Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands

Submitted July 10, 2009 ; accepted in final form August 7, 2009

Peroxisome proliferator-activated receptor- (PPAR-) 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- 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- 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- may be a key regulator of blood-brain barrier permeability and a potential therapeutic target during hypertension.

cerebral veins; acute hypertension; hydraulic conductivity