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Co‐releasing molecules attenuate placental ischemia‐induced hypertension in pregnant rats (1084.4)
Author(s) -
George Eric,
Stec David,
Granger Joey
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.1084.4
Subject(s) - preeclampsia , ischemia , endocrinology , medicine , blood pressure , placenta , downregulation and upregulation , perfusion , ex vivo , in vivo , pregnancy , chemistry , biology , fetus , biochemistry , microbiology and biotechnology , gene , genetics
Preeclampsia is a serious complication of pregnancy marked by hypertension and maternal endothelial dysfunction. Recently we have published a series of studies demonstrating that induction of heme oxygenase‐1 (HO‐1) could attenuate many of the maternal symptoms of preeclampsia in a rodent model of placental ischemia induced by Reductions on Uterine Perfusion Pressure (RUPP). We have further shown that the individual metabolites of HO‐1, namely CO and bilirubin, both downregulate hypoxia‐induced production of known placental derived pathogenic factors ex vivo . Here, we tested whether , administration of the CO‐releasing molecule CORM‐3 could attenuate the maternal symptoms of placental ischemia. In response to placental ischemia, rats exhibited marked increases in blood pressure compared to control animals (107 ± 1 vs 136 ± 2mmHg, p<0.05). Interestingly, administration of the CO‐releasing molecule CORM‐3 (5mg/kg i.v., qd) significantly decreased blood pressure in both normal pregnant (95 ± 2mmHg) and RUPP (113 ± 1) animals compared to their respective controls. Interestingly, while CORM‐3 had no significant effect on placental VEGF levels, the placental level of the VEGF antagonist sFlt‐1 was markedly increased in control (596 ± 45 vs 1143 ±122 pg/mg, p<0.05) animals, and trended towards increases in RUPP animals (1004 ± 81 vs 1213 ± 72 pg/mg) versus respective controls. This was accompanied by a significant decrease in circulating free VEGF in both Control (527 ± 30 vs 294 ± 9 pg/ml, p<0.05) and RUPP groups (363 ±44 vs 255 ± 23 pg/ml) suggesting that restoration of circulating angiogenic balance in these animals is not the mechanism responsible for their decreased blood pressure. Grant Funding Source : Supported by HL‐108618, HL‐51971 (JPG), HL‐088421, HL‐088421‐S1 (DES), and HL116774 (EMG).