Selective inhibition of 20-hydroxyeicosatetraenoic acid lowers blood pressure in a rat model of preeclampsia

Jessica L. Faulkner, Nicole L. Plenty, Kedra Wallace, Lorena M. Amaral, Mark W. Cunningham, Sydney Murphy, Babbette LaMarca

Research output: Contribution to journalArticlepeer-review

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 (1 mg/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.

Original languageEnglish (US)
Pages (from-to)108-113
Number of pages6
JournalProstaglandins and Other Lipid Mediators
Volume134
DOIs
StatePublished - Jan 2018
Externally publishedYes

Keywords

  • 20-HETE
  • Placental ischemia
  • Preeclampsia
  • RUPP rat

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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