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Inhibition of PPARγ during pregnancy causes inward remodeling of brain parenchymal arterioles
Author(s) -
Cipolla Marilyn J.,
Chan SiuLung,
Chapman Abbie C.,
Godfrey Julie A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.979.4
Subject(s) - medicine , pregnancy , endocrinology , parenchyma , lumen (anatomy) , arteriole , preeclampsia , edema , chemistry , microcirculation , biology , pathology , genetics
We previously showed that pregnancy causes outward remodeling of brain parenchymal arterioles (PA) and decreased small vessel resistance in the maternal brain, an effect that could contribute to hemorrhage and edema during conditions such as eclampsia. In the present study, we hypothesized that the mechanism by which pregnancy causes outward remodeling is through activation of PPARγ, a ligand activated transcription factor expressed in vascular cells and shown to be highly activated during pregnancy. Female SD rats were either nonpregnant (NP;n=7), late‐pregnant (LP;d20;n=7) or LP and treated with the PPARγ inhibitor GW9662 (10mg/kg/day) in food for the last 10 days of gestation (LP+GW;n=8). Brain PA were dissected, mounted in an arteriograph chamber and treated with papaverine (0.1mM) and diltiazem (10 −5 M) for measurements of passive diameter and wall thickness at pressures from 5–200 mmHg. Pregnancy caused significant outward hypotrophic remodeling of PA compared to NP, an effect that was reversed by inhibition of PPARγ. Lumen diameter and wall thickness of PA from NP, LP and LP+GW at 40 mmHg was (μm): 78±3 and 8.6±0.5, 92±4 and 6.6±0.4 (p<0.05 vs. NP and LP+GW), and 80±5 and 8.8±0.5 (ns vs. NP;p<0.05 vs. LP). There were no differences in outer diameter between groups. These results suggest that the underlying mechanism by which pregnancy causes outward hypotrophic remodeling of PA is due to PPARγ activation.