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Uterine artery smooth muscle contractions are mediated by PKC and NO signaling mechanisms in diet‐induced obese pregnant rats (700.8)
Author(s) -
Goulopoulou Styliani,
Hannan Johanna,
Webb R. Clinton
Publication year - 2014
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.28.1_supplement.700.8
Subject(s) - endocrinology , medicine , uterine artery , gestation , phenylephrine , fetus , vascular smooth muscle , protein kinase c , rho associated protein kinase , pregnancy , kinase , chemistry , biology , smooth muscle , blood pressure , biochemistry , genetics
Pre‐existing obesity increases the risk of maternal and fetal complications during gestation and is associated with systemic vascular dysfunction. We hypothesized that diet‐induced obesity would impair uterine artery contractile responses in pregnant rats. Female rats were fed for 3 weeks prior to pregnancy and throughout gestation either normal chow (LN‐Preg, n=8) or normal chow plus lard and liquid sucrose (OB‐Preg, n=8). Contractile responses to phenylephrine (PE, 10 ‐8 – 3x10 ‐5 M) were measured in isolated uterine arterial segments in late pregnancy, in the presence and absence of inhibitors of ERK1/2 (PD98059, 10 ‐5 M), Rho kinase (ROCK, Y27632: 10 ‐6 M), protein kinase C (PKC, BIM: 10 ‐6 M) and nitric oxide synthase (NOS, L‐NAME: 10 ‐4 M). OB‐Preg uterine arteries had reduced sensitivity to PE compared to LN‐Preg arteries. Inhibition of PKC reduced sensitivity to PE in OB‐Preg but not in LN‐Preg uterine arteries (‐log EC50, OB‐Preg, PE: 5.75 ± 0.087 vs. PE+BIM: 5.35 ± 0.128, p<0.05; LN‐Preg, PE: 6.07 ± 0.086, PE+BIM: 5.99 ± 0.119, p>0.05), whereas inhibition of ERK1/2 or ROCK reduced sensitivity to PE in both groups. NOS inhibition increased contractile responses to PE in OB‐Preg arteries to a greater extend as compared to LN‐Preg vessels and abolished the differences between groups ( ‐log EC50 in the presence of L‐NAME, OB‐Preg, 6.19 ± 0.103 vs. LN‐Preg, 6.19 ± 0.079, p>0.05). Pre‐existing obesity reduces uterine artery contractile responses to α 1 adrenergic stimulation in late pregnancy and this response is mediated by PKC and NO signaling mechanisms. Grant Funding Source : Supported by NIH, SWHR