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Review
. 2014 Jan-Feb;22(1):1-12.
doi: 10.1097/CRD.0b013e3182961659.

20-HETE and blood pressure regulation: clinical implications

Cheng-Chia Wu  1 , Tanush Gupta, Victor Garcia, Yan Ding, Michal L Schwartzman
Affiliations
Review

20-HETE and blood pressure regulation: clinical implications

Cheng-Chia Wu et al. Cardiol Rev. 2014 Jan-Feb.

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.

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Conflict of interest statement

The authors have no conflicts of interest to report.

Figures

FIGURE 1
FIGURE 1
Postulated mechanisms underlying the prohypertensive actions of 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). ACE indicates angiotensin-converting enzyme; AGT, angiotensinogen; Ang II, angiotensin II; AT1R, angiotensin type 1 receptor; CYP, cytochrome P450; EC, endothelial cell; IKK, IκB kinase; Kca, calcium-activated potassium channel; NF-κB, nuclear factor-kappa B; NO, nitric oxide; O2−, superoxide; VSMC, vascular smooth muscle cell.
See this image and copyright information in PMC

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