RGD Reference Report - Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension. - Rat Genome Database

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Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension.

Authors: Manhiani, M  Quigley, JE  Knight, SF  Tasoobshirazi, S  Moore, T  Brands, MW  Hammock, BD  Imig, JD 
Citation: Manhiani M, etal., Am J Physiol Renal Physiol. 2009 Sep;297(3):F740-8. Epub 2009 Jun 24.
RGD ID: 5688730
Pubmed: PMID:19553349   (View Abstract at PubMed)
PMCID: PMC2739707   (View Article at PubMed Central)
DOI: DOI:10.1152/ajprenal.00098.2009   (Journal Full-text)

Inhibition of soluble epoxide hydrolase (sEH) has been shown to be renal protective in rat models of salt-sensitive hypertension. Here, we hypothesize that targeted disruption of the sEH gene (Ephx2) prevents both renal inflammation and injury in deoxycorticosterone acetate plus high salt (DOCA-salt) hypertensive mice. Mean arterial blood pressure (MAP) increased significantly in the DOCA-salt groups, and MAP was lower in Ephx2-/- DOCA-salt (129 +/- 3 mmHg) compared with wild-type (WT) DOCA-salt (145 +/- 2 mmHg) mice. Following 21 days of treatment, WT DOCA-salt urinary MCP-1 excretion increased from control and was attenuated in the Ephx2-/- DOCA-salt group. Macrophage infiltration was reduced in Ephx2-/- DOCA-salt compared with WT DOCA-salt mice. Albuminuria increased in WT DOCA-salt (278 +/- 55 microg/day) compared with control (17 +/- 1 microg/day) and was blunted in the Ephx2-/- DOCA-salt mice (97 +/- 23 microg/day). Glomerular nephrin expression demonstrated an inverse relationship with albuminuria. Nephrin immunofluorescence was greater in the Ephx2-/- DOCA-salt group (3.4 +/- 0.3 RFU) compared with WT DOCA-salt group (1.1 +/- 0.07 RFU). Reduction in renal inflammation and injury was also seen in WT DOCA-salt mice treated with a sEH inhibitor {trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid; tAUCB}, demonstrating that the C-terminal hydrolase domain of the sEH enzyme is responsible for renal protection with DOCA-salt hypertension. These data demonstrate that Ephx2 gene deletion decreases blood pressure, attenuates renal inflammation, and ameliorates glomerular injury in DOCA-salt hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOEphx2 (Mus musculus)5688730; 5688730 RGD 
hypertension  IMP 5688730 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ephx2  (epoxide hydrolase 2)

Genes (Mus musculus)
Ephx2  (epoxide hydrolase 2, cytoplasmic)

Genes (Homo sapiens)
EPHX2  (epoxide hydrolase 2)


Additional Information