Renal Cytochrome P450-Derived Eicosanoids and Hypertension

Mong-Heng      Wang

Abstract

The cytochrome P450 (CYP) monooxygenase system represents a major metabolic pathway of arachidonic acid in the kidney. The primary CYP monooxygenase-derived arachidonic acid metabolites (eicosanoids) in renal tubular and vascular tissues are hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs), which are further metabolized by epoxide hydrolase to dihydroxyeicosatrienoic acids (DHETs). CYP-derived eicosanoids have been shown to affect vascular tone and tubular epithelial transport, contribute to the regulation of renal function, and participate in the long-term control of blood pressure. This review will focus on the biochemistry, pharmacology, and physiological significance of the CYP-derived eicosanoids in the mammalian kidney. In addition, we will also discuss the role of these metabolites in pregnancy- and obesity-induced hypertension in animal models, and in human hypertension.

Keywords: Eicosanoids, cytochrome P450, 20-HETE, EET, DHET, kidney, renal function, hypertension