title: Epoxyeicosatrienoic Acid inhibition alters renal hemodynamics during pregnancy.
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.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Hsin-Hsin
authors.initials: HH
authors.lastname: Chang
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.forename: D Sudarshan
authors.initials: DS
authors.lastname: Reddy
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.forename: John R
authors.initials: JR
authors.lastname: Falck
authors.forename: Mong-Heng
authors.initials: MH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology*; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D010105:Oxygenases / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; C000717351:Cyp2c23 protein, rat; D004852:Epoxy Compounds; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2