Selective inhibition of 20-hydroxyeicosatetraenoic acid lowers blood pressure in a rat model of preeclampsia
| Autor: | Sydney R. Murphy, Kedra Wallace, Babbette LaMarca, Nicole L. Plenty, Mark W. Cunningham, Lorena M. Amaral, Jessica L. Faulkner |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Rat model Amidines Blood Pressure 030204 cardiovascular system & hematology Selective inhibition Biochemistry Article Preeclampsia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P-450 Enzyme System Pre-Eclampsia Pregnancy Internal medicine Uterine perfusion Hydroxyeicosatetraenoic Acids medicine Animals Pharmacology business.industry Cell Biology Metabolism medicine.disease 20-Hydroxyeicosatetraenoic acid Rats Disease Models Animal 030104 developmental biology Endocrinology Blood pressure chemistry cardiovascular system Gestation Female lipids (amino acids peptides and proteins) business circulatory and respiratory physiology |
| Zdroj: | Prostaglandins & Other Lipid Mediators. 134:108-113 |
| ISSN: | 1098-8823 |
| DOI: | 10.1016/j.prostaglandins.2017.09.004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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