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.
|Number of pages||6|
|Journal||Prostaglandins and Other Lipid Mediators|
|State||Published - Jan 2018|
- Placental ischemia
- RUPP rat