Soluble epoxide hydrolase inhibitor, AUDA, prevents early salt-sensitive hypertension

Jing Li, Mairead A. Carroll, Praveen N. Chander, J R Falck, Bhavani Sangras, Charles T. Stier

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

In stroke-prone spontaneously hypertensive rats (SHRSP) end-organ damage is markedly accelerated by high-salt (HS) intake. Since epoxyeicosatrienoic acids (EETs) possess vasodepressor and natriuretic activities, we examined whether a soluble epoxide hydrolase (sEH) inhibitor, 12-(3-adamantan-1-yl-ureido)- dodecanoic acid (AUDA), to inhibit the metabolism of EETs, would protect against pathologic changes in SHRSP. Seven-week-old male SHRSP were treated as follows: normal salt (NS), NS + AUDA, HS and HS + AUDA. Systolic blood pressure (SBP) (205 +/- 4 v 187 +/- 7 mmHg) and proteinuria (3.7 +/- 0.2 v 2.6 +/- 0.2 mg/6 h), but not plasma EETs (11.0 +/-0.9 v 9.7 +/- 1.1 ng/ml), were significantly increased at 9 weeks of age in HS v NS SHRSP. HS was associated with fibrinoid degeneration and hypertrophy of arterioles in the kidney and perivascular fibrosis and contraction band necrosis in the heart. AUDA ameliorated these early salt-dependent changes in saline-drinking SHRSP and increased plasma levels of EETs but did not affect water and electrolyte excretion. sEH inhibition may provide a therapeutic strategy for treating salt-sensitive hypertension and its sequelae.

Original languageEnglish (US)
Pages (from-to)3480-3487
Number of pages8
JournalFrontiers in Bioscience
Volume13
Issue number9
DOIs
Publication statusPublished - 2008

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Keywords

  • Epoxyeicosatrienoic acid
  • Salt-sensitive hypertension
  • Soluble epoxide hydrolase inhibition
  • Stroke-prone spontaneously hypertensive rats

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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