{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:47:08Z","timestamp":1777434428067,"version":"3.51.4"},"reference-count":64,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs is contraindicated in hypertension, as it may reduce glomerular filtration rate (GFR) and renal blood flow. However, the identity of the specific eicosanoid and receptor underlying these effects is not known. We hypothesized that vascular smooth muscle prostaglandin E2 (PGE2) E-prostanoid 4 (EP4) receptor deletion predisposes to renal injury\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    unchecked vasoconstrictive actions of angiotensin II (AngII) in a hypertension model. Mice with inducible vascular smooth muscle cell (VSMC)-specific EP4 receptor deletion were generated and subjected to AngII-induced hypertension.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    EP4 deletion was verified by PCR of aorta and renal vessels, as well as functionally by loss of PGE2-mediated mesenteric artery relaxation. Both AngII-treated groups became similarly hypertensive, whereas albuminuria, foot process effacement, and renal hypertrophy were exacerbated in AngII-treated EP4\n                    <jats:sup>VSMC\u2212\/\u2212<\/jats:sup>\n                    but not in EP4\n                    <jats:sup>VSMC+\/+<\/jats:sup>\n                    mice and were associated with glomerular scarring, tubulointerstitial injury, and reduced GFR. AngII-treated EP4\n                    <jats:sup>VSMC\u2212\/\u2212<\/jats:sup>\n                    mice exhibited capillary damage and reduced renal perfusion as measured by fluorescent bead microangiography and magnetic resonance imaging, respectively. NADPH oxidase 2 (Nox2) expression was significantly elevated in AngII-treated EP4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. EP4-receptor silencing in primary VSMCs abolished PGE2 inhibition of AngII-induced Nox2 mRNA and superoxide production.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    These data suggest that vascular EP4 receptors buffer the actions of AngII on renal hemodynamics and oxidative injury.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    <\/jats:bold>\n                    <jats:italic toggle=\"yes\">:<\/jats:italic>\n                    EP4 agonists may, therefore, protect against hypertension-associated kidney damage.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                    . 25, 642\u2013656.\n                  <\/jats:p>","DOI":"10.1089\/ars.2015.6592","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T07:05:02Z","timestamp":1464764702000},"page":"642-656","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Vascular Smooth Muscle-Specific EP4 Receptor Deletion in Mice Exacerbates Angiotensin II-Induced Renal Injury"],"prefix":"10.1177","volume":"25","author":[{"given":"Jean-Francois","family":"Thibodeau","sequence":"first","affiliation":[{"name":"The Ottawa Hospital","place":["Canada"]},{"name":"University of Ottawa","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chet E.","family":"Holterman","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"He","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Carter","sequence":"additional","affiliation":[{"name":"University of Ottawa","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory O.","family":"Cron","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi C.","family":"Boisvert","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital","place":["Canada"]},{"name":"University of Ottawa","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled S.","family":"Abd-Elrahman","sequence":"additional","affiliation":[{"name":"University of Ottawa","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolynn J.","family":"Hsu","sequence":"additional","affiliation":[{"name":"University of Ottawa","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen S.G.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"University of Ottawa","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher R.J.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital","place":["Canada"]},{"name":"University of Ottawa","place":["Canada"]},{"name":"The Ottawa Hospital","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,10,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024695"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00590.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.038075"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.199026"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200001000-00005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.1.F12"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20130808"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.016"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90718.2008"},{"issue":"1","key":"e_1_3_3_11_2","first-page":"F68","article-title":"Prostaglandin interactions with angiotensin, norepinephrine, and thromboxane in rat renal vasculature","volume":"262","author":"Chatziantoniou C","year":"1992","unstructured":"Chatziantoniou C, and Arendshorst WJ. Prostaglandin interactions with angiotensin, norepinephrine, and thromboxane in rat renal vasculature. Am J Physiol, 262(1 Pt 2): F68\u2013F76, 1992.","journal-title":"Am J Physiol"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198403013100905"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(86)90928-9"},{"issue":"6","key":"e_1_3_3_14_2","first-page":"F779","article-title":"Effects of prostaglandins on vasoconstrictor action in isolated renal arterioles","volume":"248","author":"Edwards RM","year":"1985","unstructured":"Edwards RM. Effects of prostaglandins on vasoconstrictor action in isolated renal arterioles. Am J Physiol, 248(6 Pt 2): F779\u2013F784, 1985.","journal-title":"Am J Physiol"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1081\/JDI-100104719"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00054.2011"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00201.2005"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e32834d9d75"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.20"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002192"},{"key":"e_1_3_3_21_2","first-page":"357","article-title":"Angiotensin II: preferential efferent constriction?","volume":"9","author":"Heller J","year":"1986","unstructured":"Heller J, and Horacek V. Angiotensin II: preferential efferent constriction?. Ren Physiol, 9: 357\u2013365, 1986.","journal-title":"Ren Physiol"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.088948"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.2188\/jea.JE2007413"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.183301"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000035087.11758.ED"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-011-0492-3"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00183.2005"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/5583"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.59.3.3"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101121"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.184291"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46279"},{"key":"e_1_3_3_33_2","unstructured":"This reference has been deleted."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(73)90097-X"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1268-0"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000019782.37851.BF"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2013.58"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2013.85"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-365825"},{"issue":"6","key":"e_1_3_3_40_2","first-page":"F850","article-title":"Vasoconstriction of outer medullary vasa recta by angiotensin II is modulated by prostaglandin E2","volume":"266","author":"Pallone TL","year":"1994","unstructured":"Pallone TL. Vasoconstriction of outer medullary vasa recta by angiotensin II is modulated by prostaglandin E2. Am J Physiol, 266(6 Pt 2): F850\u2013F857, 1994.","journal-title":"Am J Physiol"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00036.2005"},{"key":"e_1_3_3_42_2","first-page":"e372","article-title":"Interaction between antihypertensives and NSAIDs in primary care: a controlled trial","volume":"15","author":"Pavlicevic I","year":"2008","unstructured":"Pavlicevic I, , Kuzmanic M, , Rumboldt M, , and Rumboldt Z. Interaction between antihypertensives and NSAIDs in primary care: a controlled trial. Can J Clin Pharmacol, 15: e372\u2013e382, 2008.","journal-title":"Can J Clin Pharmacol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1993.00410040045007"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00512.2011"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.4.F755"},{"issue":"6","key":"e_1_3_3_46_2","first-page":"F850","article-title":"Prostaglandins buffer ANG II-mediated increases in cytosolic calcium in preglomerular VSMC","volume":"277","author":"Purdy KE","year":"1999","unstructured":"Purdy KE, and Arendshorst WJ. Prostaglandins buffer ANG II-mediated increases in cytosolic calcium in preglomerular VSMC. Am J Physiol, 277(6 Pt 2): F850\u2013F858, 1999.","journal-title":"Am J Physiol"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00324.2003"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701214200"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp098"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.20048"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8461"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1159\/000329229"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00024.2008"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.3.723"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R600038200"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.6.663"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000203161.02046.8d"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.08.022"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000090747.59919.D2"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03654"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20448"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000258106.74139.25"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00808.x"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000140924.91479.03"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81550"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2015.6592","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ars.2015.6592","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2015.6592","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:53:48Z","timestamp":1777377228000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/ars.2015.6592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":64,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1089\/ars.2015.6592"],"URL":"https:\/\/doi.org\/10.1089\/ars.2015.6592","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]}}}