Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase
Article
Article Title | Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase |
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ERA Journal ID | 2172 |
Article Category | Article |
Authors | Loch, David (Author), Hoey, Andrew (Author), Morisseau, Christophe (Author), Hammock, Bruce O. (Author) and Brown, Lindsay (Author) |
Journal Title | Cell Biochemistry and Biophysics |
Journal Citation | 47 (1), pp. 87-98 |
Number of Pages | 12 |
Year | 2007 |
Place of Publication | Totowa, NJ. United States |
ISSN | 1085-9195 |
1559-0283 | |
Web Address (URL) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892223/?tool=pubmed |
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. |
Keywords | hypertension; prevention; DOCA-salt rats; inhibitor of soluble epoxide hydrolase |
ANZSRC Field of Research 2020 | 310999. Zoology not elsewhere classified |
320507. Metabolic medicine | |
320101. Cardiology (incl. cardiovascular diseases) | |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | University of Queensland |
Centre for Biomedical Research | |
University of California, United States |
https://research.usq.edu.au/item/9y55y/prevention-of-hypertension-in-doca-salt-rats-by-an-inhibitor-of-soluble-epoxide-hydrolase
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