Roberts TJ, Chapman AC, Cipolla MJ
PPAR{gamma} agonist rosiglitazone reverses increased cerebral venous hydraulic conductivity during hypertension. [JOURNAL ARTICLE]
Am J Physiol Heart Circ Physiol 2009 Aug 7.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists have been shown to protect the cerebral vasculature, including the blood-brain barrier (BBB). In the present study, we investigated the effect of the PPARgamma agonist rosiglitazone on changes in venous permeability during chronic hypertension induced by nitric oxide synthase (NOS) inhibition. Female Sprague Dawley rats were either treated with L-NAME (0.5 g/L in drinking water) for 5 weeks (HTN; n=8), L-NAME for 5 weeks plus the PPARgamma agonist rosiglitazone (20 mg/kg in food) for the last 3 weeks (HTN + Rosi; n=5), L-NAME for 5 weeks plus the superoxide dismutase mimetic Tempol (1mM in drinking water) for the last 3 weeks (HTN + Tempol; n=8), or untreated controls (CTL; n=9). Fluid filtration (Jv/S) and hydraulic conductivity (Lp) 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 Jv/S by 2.2 fold and Lp by 3.2 fold. Rosiglitazone treatment after 2 weeks of hypertension completely reversed the increased Jv/S and Lp that occurred during hypertension whereas Tempol had no effect. These results demonstrate that rosiglitazoine 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 PPARgamma may be a key regulator of BBB permeability and a potential therapeutic target during hypertension. Key words: cerebral veins, hypertension, blood-brain barrier, PPARgamma.
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