title: Increased blood pressure in mice lacking cytochrome P450 2J5.
abstract: The cytochrome P450 (CYP) enzymes participate in a wide range of biochemical functions, including metabolism of arachidonic acid and steroid hormones. Mouse CYP2J5 is abundant in the kidney where its products, the cis-epoxyeicosatrienoic acids (EETs), modulate sodium transport and vascular tone. To define the physiological role of CYP2J5 in the kidney, knockout mice were generated using a conventional gene targeting approach. Cyp2j5 (-/-) mice develop normally and exhibit no overt renal pathology. While renal EET biosynthesis was apparently unaffected by the absence of CYP2J5, deficiency of this CYP in female mice was associated with increased blood pressure, enhanced proximal tubular transport rates, and exaggerated afferent arteriolar responses to angiotensin II and endothelin I. Interestingly, plasma 17beta-estradiol levels were reduced in female Cyp2j5 (-/-) mice and estrogen replacement restored blood pressure and vascular responsiveness to normal levels. There was no evidence of enhanced estrogen metabolism, or altered expression or activities of steroidogenic enzymes in female Cyp2j5 (-/-) mice, but their plasma levels of luteinizing hormone and follicle stimulating hormone were inappropriately low. Together, our findings illustrate a sex-specific role for CYP2J5 in regulation of blood pressure, proximal tubular transport, and afferent arteriolar responsiveness via an estrogen-dependent mechanism.
authors: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors: Krairerk
authors: K
authors: Athirakul
authors: J Alyce
authors: JA
authors: Bradbury
authors: Joan P
authors: JP
authors: Graves
authors: Laura M
authors: LM
authors: DeGraff
authors: Jixiang
authors: J
authors: Ma
authors: Yun
authors: Y
authors: Zhao
authors: John F
authors: JF
authors: Couse
authors: Raymond
authors: R
authors: Quigley
authors: David R
authors: DR
authors: Harder
authors: Xueying
authors: X
authors: Zhao
authors: John D
authors: JD
authors: Imig
authors: Theresa L
authors: TL
authors: Pedersen
authors: John W
authors: JW
authors: Newman
authors: Bruce D
authors: BD
authors: Hammock
authors: Alan J
authors: AJ
authors: Conley
authors: Kenneth S
authors: KS
authors: Korach
authors: Thomas M
authors: TM
authors: Coffman
authors: Darryl C
authors: DC
authors: Zeldin
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000235:genetics*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency*; D019332:Endothelin-1 / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007687:Kidney Tubules, Proximal / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D010053:Ovary / Q000502:physiology; D012737:Sex Factors; D013739:Testosterone / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C000717352:Cyp2j5 protein, mouse; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016718:Arachidonic Acid; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2