NYMC Faculty Publications

20-HETE and Blood Pressure Regulation: Clinical Implications

Author Type(s)

Faculty

DOI

10.1097/CRD.0b013e3182961659

Journal Title

Cardiology in Review

First Page

1

Last Page

12

Document Type

Article

Publication Date

1-1-2014

Department

Pharmacology

Keywords

Blood Pressure, Cytochrome P-450 CYP4A, Cytochrome P-450 Enzyme System, Cytochrome P450 Family 4, Endothelium, Vascular, Humans, Hydroxyeicosatetraenoic Acids, Hypertension, Kidney Tubules, Peptidyl-Dipeptidase A, Polymorphism, Genetic, Renin-Angiotensin System

Disciplines

Medicine and Health Sciences

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.

Link to Full Text

Share

COinS