| Literature DB >> 28951260 |
Jessica L Faulkner1, Nicole L Plenty2, Kedra Wallace2, Lorena M Amaral1, Mark W Cunningham1, Sydney Murphy1, Babbette LaMarca3.
Abstract
Little is currently known of the role(s) of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) in hypertensive pregnancies. We hypothesized that specific inhibition of 20-HETE would attenuate increases in blood pressure in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Specific 20-HETE synthesis inhibitor HET0016 (1mg/kg) was administered daily to RUPP rats from gestational days 14-18. Blood pressure (BP) increased in RUPP rats and was decreased with HET0016 administration. BP was unchanged in NP+HET0016 rats. Fetal death greatly increased in RUPP rats and was reduced in RUPP+HET0016 rats. 20-HETE levels increased modestly in RUPP rats compared to NP and was reduced in both NP+HET0016 and RUPP+HET0016 rats. Furthermore, circulating levels of HETEs, EET, and DHETE were significantly altered between groups. HET0016 shifted CYP metabolism toward EETs, as indicated by a decrease in plasma 20-HETE:EETs in RUPP+HET0016 rats compared to RUPP. In conclusion, 20-HETE inhibition in RUPP rats reduces BP and fetal death, and is associated with an increase in EET/20-HETE ratio.Entities:
Keywords: 20-HETE; Placental ischemia; Preeclampsia; RUPP rat
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Year: 2017 PMID： 28951260 PMCID： PMC5902033 DOI： 10.1016/j.prostaglandins.2017.09.004
Source DB: PubMed Journal: Prostaglandins Other Lipid Mediat ISSN： 1098-8823 Impact factor: 3.072