Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase

David Loch, Andrew Hoey, Christophe Morisseau, Bruce O. Hammock, Lindsay Brown

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Cyclooxygenase and lipoxygenase metabolism of arachidonic acid produces compounds important in cardiovascular control. Further, arachidonic acid can be metabolised by cytochrome p450 to produce epoxyeicosatrienoic acids (EETs). These derivatives are inactivated by soluble epoxide hydrolase (sEH). The potential role of these EETs in hypertension and cardiac remodelling has been determined using the selective sEH inhibitor, N-adamantyl-N'-dodecylurea (ADU), in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Experiments were performed on male Wistar rats following uninephrectomy alone (UNX rats) or uninephrectomy with administration of DOCA (25 mg every fourth day subcutaneously) and 1% NaCl in drinking water (DOCA-salt rats). ADU (10 mg/kg/d subcutaneously) was administered for 2 wk starting 2 wk after surgery. Cardiovascular structure and function were determined using organ wet weights, histological analysis of collagen and inflammation, isolated heart and thoracic aortic ring preparations, and electrophysiological measurements. DOCA-salt hypertensive rats developed hypertension, hypertrophy, perivascular and interstitial fibrosis, endothelial dysfunction, and prolongation of the cardiac action potential duration within 4 wk. Administration of ADU prevented the further increase in systolic blood pressure and left-ventricular wet weight and normalized endothelial function. ADU treatment did not change inflammatory cell infiltration, collagen deposition, or cardiac action potential duration. EETs may be involved in the development of hypertension and endothelial dysfunction in DOCA-salt rats, but not in excessive collagen deposition or electrophysiological abnormalities.

Original languageEnglish (US)
Pages (from-to)87-97
Number of pages11
JournalCell Biochemistry and Biophysics
Volume47
Issue number1
StatePublished - Jan 2007

Keywords

  • DOCA-salt rats
  • Epoxyeicosatrienoic acids (EETs)
  • Hypertension
  • Remodeling
  • Soluble epoxide hydrolase (sEH)

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Biophysics

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  • Cite this

    Loch, D., Hoey, A., Morisseau, C., Hammock, B. O., & Brown, L. (2007). Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase. Cell Biochemistry and Biophysics, 47(1), 87-97.