Arachidonic acid monooxygenase

Genetic and biochemical approaches to physiological/pathophysiological relevance

Jorge H. Capdevila, Wenhui Wang, J R Falck

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Studies with rat genetic models of hypertension pointed to roles for the CYP2C and CYP4A arachidonic acid epoxygenases and ω-hydroxylases in tubular transport, hemodynamics, and blood pressure control. Further progress in defining their physiological functions and significance to human hypertension requires conclusive identifications of the relevant genes and proteins. Here we discuss unequivocal evidence of roles for the murine Cyp4a14, Cyp4a10, and Cyp2c44 genes in the pathophysiology of hypertension by showing that: (a) Cyp4a14(-/-) mice develop sexually dimorphic hypertension associated with renal vasoconstriction, and up-regulated expression of Cyp4a12a and pro-hypertensive 20-hydroxyeicosatetraenoic acid (20-HETE) levels, and b) Cyp4a10(-/-) and Cyp2c44(-/-) mice develop salt sensitive hypertension linked to downregulation or lack of the Cyp2c44 epoxygenase, reductions in anti-hypertensive epoxyeicosatrienoic acids (EETs), and increases in distal sodium reabsorption. Based on these studies, the human CYP4A11 and CYPs 2C8 and 2C9 genes and their products are identified as potential candidates for studies of the molecular basis of human hypertension.

Original languageEnglish (US)
Article number6122
Pages (from-to)40-49
Number of pages10
JournalProstaglandins and Other Lipid Mediators
Volume120
DOIs
StatePublished - Jul 1 2015

Fingerprint

Mixed Function Oxygenases
Arachidonic Acid
Molecular Biology
Cytochrome P-450 CYP4A
Genes
Hypertension
Pressure control
Blood pressure
Hemodynamics
Antihypertensive Agents
Rats
Salts
Sodium
Acids
Proteins
Genetic Models
Vasoconstriction
Down-Regulation
Blood Pressure
Kidney

Keywords

  • 20-HETE
  • Arachidonic acid
  • EET
  • Epoxygenase
  • Hypertension
  • P450

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Cite this

Arachidonic acid monooxygenase : Genetic and biochemical approaches to physiological/pathophysiological relevance. / Capdevila, Jorge H.; Wang, Wenhui; Falck, J R.

In: Prostaglandins and Other Lipid Mediators, Vol. 120, 6122, 01.07.2015, p. 40-49.

Research output: Contribution to journalArticle

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