The role of the cytochrome P450-dependent metabolites of arachidonic acid in blood pressure regulation and renal function: a review.
Arachidonic acid metabolism through the cytochrome P450-dependent monooxygenase system has been the subject of considerable research interest over the last several years. This article reviews the biological actions of the metabolites generated through this pathway and explores their role in the regulation of renal function and systemic blood pressure. Arachidonic acid is metabolized by the cytochrome P450-dependent monooxygenase system in three ways: epoxidation, resulting in the formation of 5,6-, 8,9-, 11,12-, 14,15-epoxyeicosatrienoic acids; allylic oxidation, resulting in the formation of 5,8,9,11,12,15-hydroxyeicosatetraenoic acids (HETE); and hydroxylation, resulting in the formation of 19,20-HETEs and 20-carboxyl arachidonic acid. Elements of this pathway have been localized in the kidney and several extrarenal sites. Vasodilation, vasoconstriction, inhibition of Na+,K+-ATPase, inhibition of ion transport and modulation of cell growth have been some of the diverse physiological actions demonstrated by metabolites produced by this pathway. As a physiological correlate of these properties, considerable evidence has accumulated regarding the role of the cytochrome P450-dependent metabolites of arachidonic acid in the pathogenesis of hypertension in the spontaneously hypertensive rat. Data in humans are limited, but in small studies increased production of these metabolites has been shown in hypertensive persons. In summary, several properties of products of this "third" pathway of arachidonic acid metabolism suggest a role in cardiovascular and renal function. Additional studies are needed to precisely define the role of this pathway in human hypertension.
Rahman
M
M
Department of Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4982, USA.
Wright
J T
JT
Douglas
J G
JG
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology; D007668:Kidney / Q000502:physiology*
D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System