Document Detail


Role of 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of vascular function in a model of hypertension and endothelial dysfunction.
MedLine Citation:
PMID:  20699631     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The objective of this study was to determine if acute inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis or reduced inactivation of epoxyeicosatrienoic acids (EETs) can correct L-N(G)-nitro-arginine-methyl-ester (L-NAME)-induced abnormal vascular reactivity in the perfused mesenteric bed and the carotid artery of spontaneously hypertensive rats (SHR). Administration of L-NAME in drinking water (80 mg/l) to SHR for 3 weeks resulted in abnormal vascular reactivity to norepinephrine and carbachol in the perfused mesenteric vascular bed and carotid artery, and significantly elevated mean arterial blood pressure (244 +/- 9 mm Hg) as compared to SHR controls drinking regular water (176 +/- 3 mm Hg). In the perfused mesenteric vascular bed, the impaired vascular responsiveness to norepinephrine was corrected by acute treatment with N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET0016), an inhibitor of 20-HETE formation, but not by 1-cyclohexyl-3-dodecyl urea (CDU), an inhibitor of soluble epoxide hydrolase. Treatment with either HET0016 or CDU did not improve impaired carbachol-induced vasodilation in the perfused mesenteric vascular bed. In the isolated carotid artery, treatment with HET0016 corrected the L-NAME-induced increase in norepinephrine-induced vasoconstriction, whereas only CDU treatment could improve impaired carbachol-induced vasodilation. Results of this study indicate that vascular function in a state of compromised nitric oxide formation is differentially modulated by 20-HETE and EETs, and that treatment with HET0016 or CDU may improve vascular function in a state of high blood pressure and endothelial dysfunction.
Authors:
Mariam H M Yousif; Ibrahim F Benter
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-10
Journal Detail:
Title:  Pharmacology     Volume:  86     ISSN:  1423-0313     ISO Abbreviation:  Pharmacology     Publication Date:  2010  
Date Detail:
Created Date:  2010-09-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  149-56     Citation Subset:  IM    
Copyright Information:
2010 S. Karger AG, Basel.
Affiliation:
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat, Kuwait. mariam@hsc.edu.kw
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