Document Detail


20-hydroxyeicosatetraeonic acid: a new target for the treatment of hypertension.
MedLine Citation:
PMID:  20930591     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Arachidonic acid is metabolized by enzymes of the CYP4A and 4F families to 20-hydroxyeicosatetraeonic acid (20-HETE), which plays an important role in the regulation of renal function, vascular tone, and the long-term control of arterial pressure. In the vasculature, 20-HETE is a potent vasoconstrictor, and upregulation of the production of this compound contributes to the elevation in oxidative stress and endothelial dysfunction and the increase in peripheral vascular resistance associated with some forms of hypertension. In kidney, 20-HETE inhibits Na transport in the proximal tubule and thick ascending loop of Henle, and deficiencies in the renal formation of 20-HETE contributes to sodium retention and development of some salt-sensitive forms of hypertension. 20-HETE also has renoprotective actions and opposes the effects of transforming growth factor β to promote proteinuria and renal end organ damage in hypertension. Several new inhibitors of the synthesis of 20-HETE and 20-HETE agonists and antagonists have recently been developed. These compounds along with peroxisome proliferator-activated receptor-α agonists that induce the renal formation of 20-HETE seem to have promise as antihypertensive agents. This review summarizes the rationale for the development of drugs that target the 20-HETE pathway for the treatment of hypertension and associated cardiovascular complications.
Authors:
Jan M Williams; Sydney Murphy; Marilyn Burke; Richard J Roman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  56     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-08     Completed Date:  2011-03-10     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  336-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / therapeutic use*
Arachidonic Acid / metabolism
Biological Transport
Blood Vessels / drug effects,  physiopathology
Disease Models, Animal
Humans
Hydroxyeicosatetraenoic Acids / agonists,  antagonists & inhibitors,  physiology*
Hypertension / drug therapy*,  metabolism,  physiopathology
Kidney / physiopathology
Molecular Targeted Therapy
Sodium / metabolism
Grant Support
ID/Acronym/Agency:
HL-29587/HL/NHLBI NIH HHS; HL-36279/HL/NHLBI NIH HHS; P01 HL029587/HL/NHLBI NIH HHS; P01 HL059996/HL/NHLBI NIH HHS; R37 HL036279/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Hydroxyeicosatetraenoic Acids; 27YG812J1I/Arachidonic Acid; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9NEZ333N27/Sodium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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