Renal epoxyeicosatrienoic acid synthesis during pregnancy

Yiqiang Zhou, Hsin Hsin Chang, Juan Du, Cong Yi Wang, Zheng Dong, Mong Heng Wang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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-1 for 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.

Original languageEnglish (US)
Pages (from-to)F221-F226
JournalAmerican Journal of Physiology - Renal Physiology
Volume288
Issue number1 57-1
DOIs
StatePublished - Jan 1 2005

Fingerprint

Kidney
Pregnancy
Acids
Blood Pressure
Fetal Weight
Eicosanoids
Nephrons
Arterioles
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Down-Regulation
Animal Models
Sodium
6-(2-propargyloxyphenyl)hexanoic acid
Hypertension
arachidonate epoxygenase
Proteins

Keywords

  • Blood pressure
  • Cytochrome P-450
  • Epoxyeicosatrienoic acids

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Renal epoxyeicosatrienoic acid synthesis during pregnancy. / Zhou, Yiqiang; Chang, Hsin Hsin; Du, Juan; Wang, Cong Yi; Dong, Zheng; Wang, Mong Heng.

In: American Journal of Physiology - Renal Physiology, Vol. 288, No. 1 57-1, 01.01.2005, p. F221-F226.

Research output: Contribution to journalArticle

Zhou, Yiqiang ; Chang, Hsin Hsin ; Du, Juan ; Wang, Cong Yi ; Dong, Zheng ; Wang, Mong Heng. / Renal epoxyeicosatrienoic acid synthesis during pregnancy. In: American Journal of Physiology - Renal Physiology. 2005 ; Vol. 288, No. 1 57-1. pp. F221-F226.
@article{beda49257f3547f4811ea4f36aef493f,
title = "Renal epoxyeicosatrienoic acid synthesis during pregnancy",
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-1 for 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.",
keywords = "Blood pressure, Cytochrome P-450, Epoxyeicosatrienoic acids",
author = "Yiqiang Zhou and Chang, {Hsin Hsin} and Juan Du and Wang, {Cong Yi} and Zheng Dong and Wang, {Mong Heng}",
year = "2005",
month = "1",
day = "1",
doi = "10.1152/ajprenal.00170.2004",
language = "English (US)",
volume = "288",
pages = "F221--F226",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1 57-1",

}

TY - JOUR

T1 - Renal epoxyeicosatrienoic acid synthesis during pregnancy

AU - Zhou, Yiqiang

AU - Chang, Hsin Hsin

AU - Du, Juan

AU - Wang, Cong Yi

AU - Dong, Zheng

AU - Wang, Mong Heng

PY - 2005/1/1

Y1 - 2005/1/1

N2 - 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-1 for 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.

AB - 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-1 for 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.

KW - Blood pressure

KW - Cytochrome P-450

KW - Epoxyeicosatrienoic acids

UR - http://www.scopus.com/inward/record.url?scp=11144249813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144249813&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00170.2004

DO - 10.1152/ajprenal.00170.2004

M3 - Article

C2 - 15383399

AN - SCOPUS:11144249813

VL - 288

SP - F221-F226

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1 57-1

ER -