Abstract
In this study we examined the expression of cytochrome P450 (CYP) 2C and CYP2J isoforms in renal proximal tubules and microvessels isolated from rats at different stages of pregnancy. We also selectively inhibited epoxyeicosatrienoic acid (EET) production by the administration of N-methanesulfonyl-6-(2- proparyloxyphenyl)hexanamide (MSPPOH 20 mg/kg/day iv) to rats during Days 14-17 of gestation and to age-matched virgin rats and determined the consequent effects on renal function. Western blot analysis showed that CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in the renal microvessels of pregnant rats on Day 12 of gestation. In the proximal tubules, CYP2C23 expression was significantly increased throughout pregnancy, while the expression of CYP2C11 was increased in early and late pregnancy and the expression of CYP2J2 was increased in middle and late pregnancy. MSPPOH treatment significantly increased pregnant rats' mean arterial pressure, renal vascular resistance, and sodium balance but significantly decreased renal blood flow, glomerular filtration rate, and urinary sodium excretion, as well as fetal pups' body weight and length. In contrast, MSPPOH treatment had no effect on renal hemodynamics or urinary sodium excretion in age-matched virgin rats. In pregnant rats, MSPPOH treatment also caused selective inhibition of renal cortical EET production and significantly decreased the expression of CYP2C11, CYP2C23, and CYP2J2 in the renal cortex, renal microvessels, and proximal tubules. These results suggest that upregulation of renal vascular and tubular EETs contributes to the control of blood pressure and renal function during pregnancy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1744-1752 |
| Number of pages | 9 |
| Journal | Experimental Biology and Medicine |
| Volume | 231 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jan 1 2006 |
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Keywords
- Arachidonic acid
- CYP2C
- Cytochrome p450
- EET
- Eicosanoids
- Epoxyeicosatrienoic acid
- Kidney
- Pregnancy
- Renal hemodynamics
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Epoxyeicosatrienoic acid inhibition alters renal hemodynamics during pregnancy. / Huang, Hui; Chang, Hsin Hsin; Xu, Yue; Reddy, D. Sudarshan; Du, Juan; Zhou, Yiqiang; Dong, Zheng; Falck, John R.; Wang, Mong-Heng.
In: Experimental Biology and Medicine, Vol. 231, No. 11, 01.01.2006, p. 1744-1752.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epoxyeicosatrienoic acid inhibition alters renal hemodynamics during pregnancy
AU - Huang, Hui
AU - Chang, Hsin Hsin
AU - Xu, Yue
AU - Reddy, D. Sudarshan
AU - Du, Juan
AU - Zhou, Yiqiang
AU - Dong, Zheng
AU - Falck, John R.
AU - Wang, Mong-Heng
PY - 2006/1/1
Y1 - 2006/1/1
N2 - In this study we examined the expression of cytochrome P450 (CYP) 2C and CYP2J isoforms in renal proximal tubules and microvessels isolated from rats at different stages of pregnancy. We also selectively inhibited epoxyeicosatrienoic acid (EET) production by the administration of N-methanesulfonyl-6-(2- proparyloxyphenyl)hexanamide (MSPPOH 20 mg/kg/day iv) to rats during Days 14-17 of gestation and to age-matched virgin rats and determined the consequent effects on renal function. Western blot analysis showed that CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in the renal microvessels of pregnant rats on Day 12 of gestation. In the proximal tubules, CYP2C23 expression was significantly increased throughout pregnancy, while the expression of CYP2C11 was increased in early and late pregnancy and the expression of CYP2J2 was increased in middle and late pregnancy. MSPPOH treatment significantly increased pregnant rats' mean arterial pressure, renal vascular resistance, and sodium balance but significantly decreased renal blood flow, glomerular filtration rate, and urinary sodium excretion, as well as fetal pups' body weight and length. In contrast, MSPPOH treatment had no effect on renal hemodynamics or urinary sodium excretion in age-matched virgin rats. In pregnant rats, MSPPOH treatment also caused selective inhibition of renal cortical EET production and significantly decreased the expression of CYP2C11, CYP2C23, and CYP2J2 in the renal cortex, renal microvessels, and proximal tubules. These results suggest that upregulation of renal vascular and tubular EETs contributes to the control of blood pressure and renal function during pregnancy.
AB - In this study we examined the expression of cytochrome P450 (CYP) 2C and CYP2J isoforms in renal proximal tubules and microvessels isolated from rats at different stages of pregnancy. We also selectively inhibited epoxyeicosatrienoic acid (EET) production by the administration of N-methanesulfonyl-6-(2- proparyloxyphenyl)hexanamide (MSPPOH 20 mg/kg/day iv) to rats during Days 14-17 of gestation and to age-matched virgin rats and determined the consequent effects on renal function. Western blot analysis showed that CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in the renal microvessels of pregnant rats on Day 12 of gestation. In the proximal tubules, CYP2C23 expression was significantly increased throughout pregnancy, while the expression of CYP2C11 was increased in early and late pregnancy and the expression of CYP2J2 was increased in middle and late pregnancy. MSPPOH treatment significantly increased pregnant rats' mean arterial pressure, renal vascular resistance, and sodium balance but significantly decreased renal blood flow, glomerular filtration rate, and urinary sodium excretion, as well as fetal pups' body weight and length. In contrast, MSPPOH treatment had no effect on renal hemodynamics or urinary sodium excretion in age-matched virgin rats. In pregnant rats, MSPPOH treatment also caused selective inhibition of renal cortical EET production and significantly decreased the expression of CYP2C11, CYP2C23, and CYP2J2 in the renal cortex, renal microvessels, and proximal tubules. These results suggest that upregulation of renal vascular and tubular EETs contributes to the control of blood pressure and renal function during pregnancy.
KW - Arachidonic acid
KW - CYP2C
KW - Cytochrome p450
KW - EET
KW - Eicosanoids
KW - Epoxyeicosatrienoic acid
KW - Kidney
KW - Pregnancy
KW - Renal hemodynamics
UR - http://www.scopus.com/inward/record.url?scp=33845236176&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845236176&partnerID=8YFLogxK
U2 - 10.1177/153537020623101112
DO - 10.1177/153537020623101112
M3 - Article
VL - 231
SP - 1744
EP - 1752
JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
SN - 1535-3702
IS - 11
ER -