PPARγ activation reverses hypertensive remodeling of cerebral arteries

Peroxisome proliferator‐activated receptor gamma (PPARγ) is expressed in vascular smooth muscle and is thought to have beneficial effects on the vasculature. We tested the hypothesis that PPARγ activation could reverse pre‐existing remodeling of cerebral arteries induced by hypertension. Female SD rats were hypertensive for 5 weeks by NOS inhibition with L‐NAME (0.5 g/ml in drinking water; HTN, n=11) and compared to untreated controls (CTL, n=7). A separate group of HTN rats were given the PPARγ activator rosiglitazone (20 mg/kg in food) after 2 weeks on L‐NAME for the remaining 3 weeks (HTN+Rosi, n=8). L‐NAME increased MAP for the entire 5 weeks in both HTN and HTN+Rosi groups vs. CTL (mmHg): 134 ± 5 and 132 ± 2 vs. 111 ± 2 (p<0.01). Elevated pressure in the HTN group was associated with inward hypertrophic remodeling of posterior cerebral arteries, demonstrated by reduced inner diameters and increased wall thickness. PPARγ activation reversed remodeling and had similar diameters and wall thickness as controls. At 75 mmHg, inner diameters of isolated arteries from CTL, HTN and HTN+Rosi were (μm): 224 ± 9, 199 ± 5 (p<0.01 vs. CTL) and 217 ± 8 (ns vs. CTL) and wall:lumen ratios were 0.04 ± 0.002, 0.06 ± 0.002 (p<0.01 vs. CTL and HTN‐Rosi) and 0.04 ± 0.002 (ns vs. CTL). These data demonstrate that PPARγ activation reverses hypertensive remodeling of cerebral arteries despite significantly elevated blood pressure.