Cytochrome P450, the arachidonic acid cascade, and hypertension

New vistas for an old enzyme system

Keiko Makita, J R Falck, Jorge H. Capdevila

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

As a participant of the endogenous arachidonic acid metabolic cascade, microsomal cytochrome P450 metabolizes the fatty acid to biologically active hydroxyeicosatetraenoic and epoxyeicosatrienoic acids. Studies from several laboratories have documented the powerful vasoactive properties of these P450-derived eicosanoids. Associated changes in cell membrane ion permeability and fluxes may provide the molecular basis underlining their vasoactivity. Furthermore, a role for the P450 arachidonic acid monooxygenase in renal physiology and pathophysiology has been suggested by: 1) an association between the activities of the arachidonic acid ω/ω-1 oxygenase and the development of hypertension in spontaneously hypertensive rats, and 2) a relationship between acquired or inherited abnormalities in the renal epoxygenase activities and/or regulation and salt-sensitive hypertension in Dahl rats. These studies provide significant evidence to indicate that microsomal P450, in addition to its recognized traditional toxicological and pharmacological roles, may also play an important physiological role in the control of tissue and body homeostasis.

Original languageEnglish (US)
Pages (from-to)1456-1463
Number of pages8
JournalFASEB Journal
Volume10
Issue number13
StatePublished - 1996

Fingerprint

arachidonic acid
cytochrome P-450
Arachidonic Acid
Cytochrome P-450 Enzyme System
hypertension
Hypertension
Rats
Enzymes
enzymes
kidneys
Inbred Dahl Rats
Cell Membrane Permeability
Kidney
Hydroxyeicosatetraenoic Acids
Oxygenases
eicosanoids
Eicosanoids
rats
Physiology
Inbred SHR Rats

Keywords

  • ω-alcohols
  • ω/ω-1 oxygenase
  • EETs
  • epoxyeicosatrienoic acid

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Cytochrome P450, the arachidonic acid cascade, and hypertension : New vistas for an old enzyme system. / Makita, Keiko; Falck, J R; Capdevila, Jorge H.

In: FASEB Journal, Vol. 10, No. 13, 1996, p. 1456-1463.

Research output: Contribution to journalArticle

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