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Cytochrome P450, the arachidonic acid cascade, and hypertension: new vistas for an old enzyme system
Author(s) -
Makita Keiko,
Falck John R.,
Capdevila Jorge H.
Publication year - 1996
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.10.13.8940291
Subject(s) - arachidonic acid , epoxygenase , cytochrome p450 , microsome , monooxygenase , chemistry , enzyme , biochemistry , endocrinology , medicine , pharmacology , biology
As a participant of the endogenous arachidonic acid metabolic cascade, microsomal cy‐tochrome P450 metabolizes the fatty acid to biologi‐cally active hydroxyeicoeatetraenoic and epoxy‐ eicosatrienoic acids. Studies from several laborato‐ries have documented the powerful vasoactive prop‐erties 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 ϕ/ϕ‐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.—Makita, K., Falck, J. R., Capdevila, J. H. Cytochrome P4S0, the arachidonic acid cascade, and hypertension: new vistas for an old enzyme system. FASEB J. 10, 1456‐1463 (1996)