Document Detail

20-HETE and furosemide-induced natriuresis in salt-sensitive essential hypertension.
MedLine Citation:
PMID:  12623983     Owner:  NLM     Status:  MEDLINE    
Cyclooxygenase metabolites of arachidonic acid modulate the natriuretic effect of furosemide. It is not known whether 20-HETE, a monooxygenase metabolite of arachidonic acid that also inhibits sodium transport, participates in the action of furosemide. We measured urine sodium (UNaV) and 20-HETE during furosemide diuresis (40 mg three times over 12 hours) in 12 salt-sensitive (SS) and 11 salt-resistant (SR), salt-replete hypertensive subjects (126+/-24 mmol/24 hours positive sodium balance produced by 160-mmol-sodium diet and 2 L saline infusion). Individual systolic blood pressure decreases from the salt-replete to the salt-depleted state were the index of salt-sensitivity. SS had low plasma renin with blunted responses to changes in salt balance, inappropriate plasma aldosterone, and an increased aldosterone/renin ratio. UNaV by furosemide was less in SS (263+/-25 mmol/12 hours) than in SR (351+/-25 mmol/12 hours, P<0.02) patients. 20-HETE was not different between SS and SR patients before (1.92+/-0.38 versus 1.37+/-0.34 microg/h) or after furosemide (1.52+/-0.27 versus 2.01+/-0.40 microg/h), but furosemide changed 20-HETE excretion in opposite direction in SR (0.63+/-0.26) versus SS (-0.40+/-0.17, P<0.005) patients. In all patients together, %Delta20-HETE by furosemide correlated with %DeltaUNaV (r=0.56, P<0.01) and negatively with salt-sensitivity of blood pressure (r=-0.55, P<0.01). In SS, Delta20-HETE by furosemide correlated with Deltaaldosterone/renin ratio (r=0.60, P<0.05), whereas 20-HETE during furosemide had a negative correlation with body mass index (r=-0.73, P<0.01). Our data suggest that 20-HETE modulates the natriuretic response to furosemide, and impaired natriuresis of SS involves a mechanism that alters the 20-HETE response to furosemide and is linked to salt-sensitivity of blood pressure.
Cheryl L Laffer; Michal Laniado-Schwartzman; Mong-Heng Wang; Alberto Nasjletti; Fernando Elijovich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-01-13
Journal Detail:
Title:  Hypertension     Volume:  41     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-07     Completed Date:  2003-04-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  703-8     Citation Subset:  IM    
Department of Medicine, Lenox Hill Hospital, New York University School of Medicine, New York, USA.
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MeSH Terms
Aldosterone / blood
Blood Pressure
Furosemide / pharmacology*
Hydroxyeicosatetraenoic Acids / urine*
Hypertension / blood,  etiology,  urine*
Natriuresis / drug effects
Renin / blood
Sodium / urine*
Sodium Chloride / administration & dosage*
Grant Support
M01 RR00073/RR/NCRR NIH HHS; P01 34300//PHS HHS
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; 52-39-1/Aldosterone; 54-31-9/Furosemide; 7440-23-5/Sodium; 7647-14-5/Sodium Chloride; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; EC

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