Document Detail


Differential regulation of natriuresis by 20-hydroxyeicosatetraenoic Acid in human salt-sensitive versus salt-resistant hypertension.
MedLine Citation:
PMID:  12566369     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Twenty-hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 metabolite of arachidonic acid that produces vasoconstriction and inhibition of renal tubular sodium transport. In Dahl rats, a 20-HETE deficiency plays a role in salt-sensitive (SS) hypertension. In humans, there are no data on regulation of 20-HETE by salt intake or on a role for this compound in SS hypertension. METHODS AND RESULTS: Thirteen salt-resistant (SR) and 13 SS hypertensive subjects had urine 20-HETE excretion measured during salt-loading and depletion. In all patients, 20-HETE was 66.6% higher in the salt-replete (1.75+/-0.25 micro g/h) than in the salt-depleted state (1.05+/-0.16, P<0.003). There was no difference in 20-HETE excretion between SR and SS patients in either state of salt balance. In SR patients, sodium excretion during salt-loading correlated with 20-HETE (r=0.61, P<0.03) but not with blood pressure. In contrast, in SS patients, sodium excretion did not correlate with 20-HETE but did correlate with blood pressure (r=0.66, P<0.02). Finally, in the SS group only, there was a negative correlation between body mass index and 20-HETE excretion (r=-0.79, P<0.002) that was present during both salt-loading and depletion. CONCLUSIONS: We demonstrate for the first time that 20-HETE excretion is regulated by salt intake in hypertension. We find a disrupted relationship between sodium excretion and 20-HETE in SS patients, which results in dependence of their salt excretion on blood pressure and may be related to the magnitude of their obesity. We conclude that salt-sensitivity of blood pressure in essential hypertension may result from impairment of a natriuretic mechanism dependent on 20-HETE.
Authors:
Cheryl L Laffer; Michal Laniado-Schwartzman; Mong-Heng Wang; Alberto Nasjletti; Fernando Elijovich
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  107     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-02-04     Completed Date:  2003-02-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  574-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Lenox Hill Hospital, New York University School of Medicine, New York, USA. claffer@lenoxhill.net
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Pressure / drug effects
Creatinine / urine
Diet, Sodium-Restricted
Female
Furosemide / therapeutic use
Humans
Hydroxyeicosatetraenoic Acids / urine*
Hypertension / diagnosis,  etiology*,  physiopathology,  therapy
Male
Middle Aged
Natriuresis / drug effects*
Obesity / physiopathology
Sodium / urine
Sodium Chloride, Dietary* / adverse effects,  diagnostic use
Grant Support
ID/Acronym/Agency:
M01 RR00073/RR/NCRR NIH HHS; P01 34300//PHS HHS
Chemical
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; 0/Sodium Chloride, Dietary; 54-31-9/Furosemide; 60-27-5/Creatinine; 7440-23-5/Sodium; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid

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


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