title: 20-HETE and blood pressure regulation: clinical implications.
abstract: 20-Hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE) is a cytochrome P450 (CYP)-derived omega-hydroxylation metabolite of arachidonic acid. 20-HETE has been shown to play a complex role in blood pressure regulation. In the kidney tubules, 20-HETE inhibits sodium reabsorption and promotes natriuresis, thus, contributing to antihypertensive mechanisms. In contrast, in the microvasculature, 20-HETE has been shown to play a pressor role by sensitizing smooth muscle cells to constrictor stimuli and increasing myogenic tone, and by acting on the endothelium to further promote endothelial dysfunction and endothelial activation. In addition, 20-HETE induces endothelial angiotensin-converting enzyme, thus, setting forth a potential feed forward prohypertensive mechanism by stimulating the renin-angiotensin-aldosterone system. With the advancement of gene sequencing technology, numerous polymorphisms in the regulatory coding and noncoding regions of 20-HETE-producing enzymes, CYP4A11 and CYP4F2, have been associated with hypertension. This in-depth review article discusses the biosynthesis and function of 20-HETE in the cardiovascular system, the pharmacological agents that affect 20-HETE action, and polymorphisms of CYP enzymes that produce 20-HETE and are associated with systemic hypertension in humans.
authors.affiliation: From the *Department of Pharmacology and Department of Medicine, New York Medical College, Valhalla, NY; †Department of Medicine, Greenwich Hospital, Greenwich, CT; and ‡Department of Medicine, New York Medical College, Valhalla, NY.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Wu
authors.forename: Tanush
authors.initials: T
authors.lastname: Gupta
authors.forename: Victor
authors.initials: V
authors.lastname: Garcia
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Michal L
authors.initials: ML
authors.lastname: Schwartzman
mesh_terms: D001794:Blood Pressure / Q000187:drug effects*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D007684:Kidney Tubules / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A; D007703:Peptidyl-Dipeptidase A