Relaxin causes selective outward remodeling of brain parenchymal arterioles via activation of peroxisome proliferator-activated receptor-γ

Brain parenchymal arterioles (PAs), but not pial arteries, undergo hypotrophic outward remodeling during pregnancy that involves peroxisome proliferator-activated receptor-gamma (PPAR gamma) activation. Relaxin, a peptide hormone produced during pregnancy, is involved in systemic and renal artery remodeling and activates PPAR gamma in vitro. Thus, we hypothesized that relaxin is involved in the selective outward remodeling of PAs through a PPAR gamma-dependent mechanism. Nonpregnant rats were treated with relaxin (4 mu g/h, osmotic minipump), relaxin plus PPAR gamma 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 mu m in vehicle; P<0.05) and inner diameter (outward remodeling; 10.6 +/- 0.5 vs. 8.0 +/- 0.6 mu m in vehicle; P<0.05) in PAs, but not in MCAs. This hypertrophic outward remodeling was prevented by GW9662 that had diameters (57 +/- 3 mu m) and wall thickness (8.6 +/- 1.0 mu m) similar to vehicle. GW9662 also prevented relaxin-induced changes in PPAR gamma 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 PPAR gamma.-Chan, S.-L., Cipolla, M. J. Relaxin causes selective outward remodeling of brain parenchymal arterioles via activation of peroxisome proliferator-activated receptor-gamma. FASEB J. 25, 3229-3239 (2011). www.fasebj.org