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Renal epoxyeicosatrienoic acid synthesis during pregnancy
- Source :
- American Journal of Physiology-Renal Physiology. 288:F221-F226
- Publication Year :
- 2005
- Publisher :
- American Physiological Society, 2005.
-
Abstract
- Epoxyeicosatrienoic acids (EETs), which belong to cytochrome P-450 (CYP)-derived eicosanoids, have been implicated to vasodilate renal arterioles, inhibit sodium transport in the nephron, and regulate blood pressure in several animal models. Because pregnancy is associated with changes of blood pressure, the aim of this study was to examine whether renal EET synthesis is altered and whether EETs are involved in blood pressure regulation during pregnancy in rats. Renal microsomal epoxygenase activity increased by 47, 97, and 63% on days 6, 12, and 19 of gestation, respectively. The elevation of epoxygenase activity during pregnancy was associated with an increase in CYP2C11, CYP2C23, and CYP2J2 protein expression on days 6, 12, and 19 of gestation. Moreover, immunohistochemical analysis showed that renal tubular CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in pregnant rats on days 6, 12, and 19 of gestation. Administration of 6-(2-propargyloxyphenyl)hexanoic acid (PPOH), a selective epoxygenase inhibitor, caused a dose-dependent inhibition of microsomal expoxygenase activity without a significant effect on ω-hydroxylase activity in female rats. Interestingly, administration of PPOH (20 mg·kg−1·day−1for 4 days starting on day 15 of pregnancy) increased blood pressure by 21 mmHg and caused a significant decrease in the body weight of fetal pups (1.3 ± 0.08 g in control vs. 1.1 ± 0.06 g in PPOH). Moreover, PPOH treatment significantly decreased renal microsomal epoxygenase activity and the expression of CYP2C11, CYP2C23, and CYP2J in pregnant rats. This study demonstrates that EET synthesis in the kidney is elevated during pregnancy, and CYP2C11, 2C23, and CYP2J2 are responsible for the change of renal EET synthesis. The inhibition results demonstrate that the downregulation of renal epoxygenase activity by PPOH causes hypertension in pregnant rats. This study suggests that EETs may contribute to the control of blood pressure during pregnancy.
- Subjects :
- medicine.medical_specialty
Cytochrome
Physiology
Sodium
Urinary system
chemistry.chemical_element
Blood Pressure
Vasodilation
Nephron
Biology
Kidney
Epoxyeicosatrienoic acid
Cytochrome P-450 CYP2J2
Rats, Sprague-Dawley
chemistry.chemical_compound
Fetus
Cytochrome P-450 Enzyme System
Biosynthesis
Pregnancy
Internal medicine
medicine
Animals
Birth Weight
Cytochrome P-450 Enzyme Inhibitors
Caproates
medicine.disease
Rats
medicine.anatomical_structure
Endocrinology
Fetal Weight
chemistry
biology.protein
Eicosanoids
Pregnancy, Animal
Female
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 288
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....487cd54066b704abfd56d04099b69214