The role of 20-HETE in androgen-mediated hypertension.

Androgen plays an important role in blood pressure regulation. Epidemiological studies have shown that men have a higher prevalence for developing hypertension than aged-matched, premenopausal women. Interestingly, postmenopausal women and women with polycystic ovary syndrome, both of which have increased endogenous androgen production, have elevated risks for hypertension suggesting that androgen may contribute to its development. Studies from our laboratory and others have provided substantial evidence that 20-hydroxyeicosatetraenoic acid (20-HETE) mediates the hypertension seen in rodents treated with androgen. 20-HETE is the cytochrome P450 (CYP)-derived ω-hydroxylated metabolite of arachidonic acid. 20-HETE plays a complex role in blood pressure regulation. In the kidney tubules, 20-HETE decreases blood pressure by promoting natriuresis, while in the microvasculature it has a pressor effect. In the microcirculation, 20-HETE participates in the regulation of vascular tone by sensitizing the smooth muscle cells to constrictor stimuli and contributes to myogenic, mitogenic and angiogenic responses. In addition, 20-HETE acts on the endothelium to promote endothelial dysfunction and endothelial activation. Recently, we have demonstrated that 20-HETE induces endothelial ACE thus setting forth a potential feed forward mechanism through activation of the renin-angiotensin-aldosterone system. In this review, we will discuss the pro-hypertensive effects of 20-HETE and its role in androgen-induced vascular dysfunction and hypertension.
AuthorsCheng-Chia Wu, Michal Laniado Schwartzman
JournalProstaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 96 Issue 1-4 Pg. 45-53 (Nov 2011) ISSN: 1098-8823 [Print] United States
PMID21722750 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Androgens
  • Hydroxyeicosatetraenoic Acids
  • Arachidonic Acid
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • Cytochrome P-450 CYP4A
  • Acetylcholinesterase
  • Acetylcholinesterase (genetics, metabolism)
  • Androgens (adverse effects, metabolism, pharmacology)
  • Animals
  • Arachidonic Acid (metabolism)
  • Blood Pressure (drug effects)
  • Cytochrome P-450 CYP4A (metabolism)
  • Endothelial Cells (metabolism)
  • Enzyme Induction (drug effects)
  • Female
  • Humans
  • Hydroxyeicosatetraenoic Acids (metabolism)
  • Hypertension (metabolism, physiopathology)
  • Kidney (metabolism, physiopathology)
  • Male
  • Mice
  • Natriuresis (drug effects)
  • Postmenopause
  • Premenopause
  • Rats
  • Renin-Angiotensin System (physiology)
  • Rodentia
  • Signal Transduction (drug effects)

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