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

Loch, David and Hoey, Andrew and Morisseau, Christophe and Hammock, Bruce O. and Brown, Lindsay (2007) Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase. Cell Biochemistry and Biophysics, 47 (1). pp. 87-98. ISSN 1085-9195


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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to published version due to publisher's copyright policy. The original publication is available at
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 18 Apr 2008 02:21
Last Modified: 14 Nov 2013 06:12
Uncontrolled Keywords: hypertension; prevention; DOCA-salt rats; inhibitor of soluble epoxide hydrolase
Fields of Research : 06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified
11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110107 Metabolic Medicine
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases

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