PPAR{gamma} Activation Prevents Hypertensive Remodeling of Cerebral Arteries and Improves Vascular Function in Female Rats

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.