Cytochrome P450, the arachidonic acid cascade, and hypertension: New vistas for an old enzyme system

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.