{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T05:27:20Z","timestamp":1794547640086,"version":"4.9.1"},"reference-count":54,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:p> 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\u2212\/\u2212 DOCA-salt (129 \u00b1 3 mmHg) compared with wild-type (WT) DOCA-salt (145 \u00b1 2 mmHg) mice. Following 21 days of treatment, WT DOCA-salt urinary MCP-1 excretion increased from control and was attenuated in the Ephx2\u2212\/\u2212 DOCA-salt group. Macrophage infiltration was reduced in Ephx2\u2212\/\u2212 DOCA-salt compared with WT DOCA-salt mice. Albuminuria increased in WT DOCA-salt (278 \u00b1 55 \u03bcg\/day) compared with control (17 \u00b1 1 \u03bcg\/day) and was blunted in the Ephx2\u2212\/\u2212 DOCA-salt mice (97 \u00b1 23 \u03bcg\/day). Glomerular nephrin expression demonstrated an inverse relationship with albuminuria. Nephrin immunofluorescence was greater in the Ephx2\u2212\/\u2212 DOCA-salt group (3.4 \u00b1 0.3 RFU) compared with WT DOCA-salt group (1.1 \u00b1 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. <\/jats:p>","DOI":"10.1152\/ajprenal.00098.2009","type":"journal-article","created":{"date-parts":[[2009,6,25]],"date-time":"2009-06-25T01:10:25Z","timestamp":1245892225000},"page":"F740-F748","source":"Crossref","is-referenced-by-count":122,"title":["Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension"],"prefix":"10.1152","volume":"297","author":[{"given":"Marlina","family":"Manhiani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey E.","family":"Quigley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F.","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Tasoobshirazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TarRhonda","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Brands","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Hammock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Imig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-008-0009-y"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01472-3"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.3.415"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1159\/000110021"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/16.3.452"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00466.2007"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.098806"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000198545.01860.90"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2003.08.060"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/46816"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2007.11.002"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007020220"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1159\/000110563"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.502179"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1161\/hc3601.095576"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Imig JD. Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases. Am J Physiol Renal Physiol 289: F496\u2013F503, 2005.","DOI":"10.1152\/ajprenal.00350.2004"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3466.2006.00169.x"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1080\/10739680701456960"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1161\/hy0202.103788"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000176237.74820.75"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000153792.29478.1d"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1021\/jm030514j"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.099499"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0056-07.2007"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.2741\/2889"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl085"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00306.2004"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070057"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1385\/CBB:47:1:87"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608057200"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1159\/000104094"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1038\/ng.129"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.8849"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.45.120403.095920"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00428.2008"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64445-8"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0437724100"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5431.1276"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100439200"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1042\/CS20080039"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-008-9071-0"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2001"},{"key":"R43","doi-asserted-by":"crossref","unstructured":"Ruiz-Ortega M, Lorenzo O, Ruperez M, Esteban V, Mezzano S, Egido J. Renin-angiotensin system and renal damage: emerging data on angiotensin II as a proinflammatory mediator. Contrib Nephrol 123\u2013137, 2001.","DOI":"10.1159\/000060153"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503279102"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000237390.92932.37"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008106200"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.061273"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(03)00049-3"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00981.2007"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.11.992"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.508325"},{"key":"R52","unstructured":"Zhao X, Yamamoto T, Newman JW, Kim IH, Watanabe T, Hammock BD, Stewart J, Pollock JS, Pollock DM, Imig JD. Soluble epoxide hydrolase inhibition protects the kidney from hypertension-induced damage. J Am Soc Nephrol 15: 1244\u20131253, 2004."},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.203"},{"key":"R54","doi-asserted-by":"crossref","unstructured":"Zoccali C, Mallamaci F, Tripepi G. Traditional and emerging cardiovascular risk factors in end-stage renal disease. Kidney Int Suppl: S105\u2013S110, 2003.","DOI":"10.1046\/j.1523-1755.63.s85.25.x"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00098.2009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:10:30Z","timestamp":1567987830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00098.2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,9]]}},"alternative-id":["10.1152\/ajprenal.00098.2009"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00098.2009","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9]]}}}