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

doi:10.1016/j.prostaglandins.2017.09.004

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 journal › Article › peer-review

4 Scopus citations

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 language	English
Pages (from-to)	108-113
Number of pages	6
Journal	Prostaglandins and Other Lipid Mediators
Volume	134
DOIs	https://doi.org/10.1016/j.prostaglandins.2017.09.004
State	Published - Jan 2018

Keywords

20-HETE
Placental ischemia
Preeclampsia
RUPP rat

Access to Document

10.1016/j.prostaglandins.2017.09.004

Cite this

@article{8a23f7b9e0234af0aefacbdf9a138d17,

title = "Selective inhibition of 20-hydroxyeicosatetraenoic acid lowers blood pressure in a rat model of preeclampsia",

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.",

keywords = "20-HETE, Placental ischemia, Preeclampsia, RUPP rat",

author = "Faulkner, {Jessica L.} and Plenty, {Nicole L.} and Kedra Wallace and Amaral, {Lorena M.} and Cunningham, {Mark W.} and Sydney Murphy and Babbette LaMarca",

note = "Funding Information: This work was supported by NIH grants HL105324 , HL124715 , HL78147 and HL51971 and HD067541 and AHA grant 14SDG20160020 . Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2018",

month = jan,

doi = "10.1016/j.prostaglandins.2017.09.004",

language = "English",

volume = "134",

pages = "108--113",

journal = "Prostaglandins and Other Lipid Mediators",

issn = "1098-8823",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Selective inhibition of 20-hydroxyeicosatetraenoic acid lowers blood pressure in a rat model of preeclampsia

AU - Faulkner, Jessica L.

AU - Plenty, Nicole L.

AU - Wallace, Kedra

AU - Amaral, Lorena M.

AU - Cunningham, Mark W.

AU - Murphy, Sydney

AU - LaMarca, Babbette

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

KW - 20-HETE

KW - Placental ischemia

KW - Preeclampsia

KW - RUPP rat

UR - http://www.scopus.com/inward/record.url?scp=85031424803&partnerID=8YFLogxK

U2 - 10.1016/j.prostaglandins.2017.09.004

DO - 10.1016/j.prostaglandins.2017.09.004

M3 - Article

C2 - 28951260

AN - SCOPUS:85031424803

SN - 1098-8823

VL - 134

SP - 108

EP - 113

JO - Prostaglandins and Other Lipid Mediators

JF - Prostaglandins and Other Lipid Mediators

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this