20-HETE and furosemide-induced natriuresis in salt-sensitive essential hypertension

Cheryl L. Laffer, Michal Laniado-Schwartzman, Mong Heng Wang, Alberto Nasjletti, Fernando Elijovich

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

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 μg/h) or after furosemide (1.52±0.27 versus 2.01±0.40 μg/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, %Δ20-HETE by furosemide correlated with %ΔUNaV (r=0.56, P<0.01) and negatively with salt-sensitivity of blood pressure (r=-0.55, P<0.01). In SS, Δ20-HETE by furosemide correlated with Aaldosterone/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.

Original languageEnglish (US)
Pages (from-to)703-708
Number of pages6
JournalHypertension
Volume41
Issue number3 II
DOIs
Publication statusPublished - Mar 1 2003
Externally publishedYes

    Fingerprint

Keywords

  • Arachidonic acid
  • Furosemide
  • Human
  • Hypertension, sodium dependent
  • Natriuresis
  • Risk factors
  • Sodium

ASJC Scopus subject areas

  • Internal Medicine

Cite this