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 mono oxygenase system has been the subject of considerable research interes t over the last several years. This article reviews the biological act ions of the metabolites generated through this pathway and explores th eir role in the regulation of renal function and systemic blood pressu re. Arachidonic acid is metabolized by the cytochrome P450-dependent m onooxygenase system in three ways: epoxidation, resulting in the forma tion of 5,6-, 8,9-, 11,12-, 14,15-epoxyeicosatrienoic acids; allylic o xidation, resulting in the formation of 5,8,9,11,12,15-hydroxyeicosate traenoic acids (HETE); and hydroxylation, resulting in the formation o f 19,20-HETEs and 20-carboxyl arachidonic acid. Elements of this pathw ay have been localized in the kidney and several extrarenal sites. Vas odilation, vasoconstriction, inhibition of Na+,K+-ATPase, inhibition o f ion transport and modulation of cell growth have been some of the di verse physiological actions demonstrated by metabolites produced by th is pathway. As a physiological correlate of these properties, consider able evidence has accumulated regarding the role of the cytochrome P45 0-dependent metabolites of arachidonic acid in the pathogenesis of hyp ertension in the spontaneously hypertensive rat. Data in humans are li mited, 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 studie s are needed to precisely define the role of this pathway in human hyp ertension. (C) 1997 American Journal of Hypertension, Ltd.