title: Relaxin causes selective outward remodeling of brain parenchymal arterioles via activation of peroxisome proliferator-activated receptor-γ.
abstract: Brain parenchymal arterioles (PAs), but not pial arteries, undergo hypotrophic outward remodeling during pregnancy that involves peroxisome proliferator-activated receptor-γ (PPARγ) activation. Relaxin, a peptide hormone produced during pregnancy, is involved in systemic and renal artery remodeling and activates PPARγ in vitro. Thus, we hypothesized that relaxin is involved in the selective outward remodeling of PAs through a PPARγ-dependent mechanism. Nonpregnant rats were treated with relaxin (4 μg/h, osmotic minipump), relaxin plus PPARγ inhibitor GW9662 (10 mg/kg/d), or vehicle for 10 d. Vascular function and structure were compared in isolated and pressurized middle cerebral arteries (MCAs) and PAs taken from the same animals. Relaxin treatment increased serum relaxin to the level of pregnancy (54 ng/ml) and increased passive wall thickness (hypertrophy; 70 ± 5 vs. 54 ± 4 μm in vehicle; P<0.05) and inner diameter (outward remodeling; 10.6 ± 0.5 vs. 8.0 ± 0.6 μm in vehicle; P<0.05) in PAs, but not in MCAs. This hypertrophic outward remodeling was prevented by GW9662 that had diameters (57 ± 3 μm) and wall thickness (8.6 ± 1.0 μm) similar to vehicle. GW9662 also prevented relaxin-induced changes in PPARγ target gene expression. These results suggest that relaxin produced during pregnancy may be partly responsible for selective remodeling of PAs during pregnancy through a mechanism involving PPARγ
authors: Department of Neurology, University of Vermont, Burlington, VT 05401 USA.
authors: Siu-Lung
authors: SL
authors: Chan
authors: Marilyn J
authors: MJ
authors: Cipolla
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