IMR Press / FBL / Volume 13 / Issue 9 / DOI: 10.2741/2942

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Soluble epoxide hydrolase inhibitor, AUDA, prevents early salt-sensitive hypertension
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1 Department of Pharmacology, New York Medical College, Valhalla, New York 10595
2 Department of Pathology, New York Medical College, Valhalla, New York 10595
3 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390

*Author to whom correspondence should be addressed.

Academic Editor: John Zhang

Front. Biosci. (Landmark Ed) 2008, 13(9), 3480–3487; https://doi.org/10.2741/2942
Published: 1 May 2008
(This article belongs to the Special Issue New frontiers in neurosurgery research)
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.

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