{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T01:27:19Z","timestamp":1778462839298,"version":"3.51.4"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,10,24]],"date-time":"2011-10-24T00:00:00Z","timestamp":1319414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Reduced NO availability has been described as a key mechanism responsible for endothelial dysfunction in atherosclerosis. We previously reported that neuronal NOS (nNOS)\u2010derived H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> is an important endothelium\u2010derived relaxant factor in the mouse aorta. The role of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and nNOS in endothelial dysfunction in atherosclerosis remains undetermined. We hypothesized that a decrease in nNOS\u2010derived H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> contributes to the impaired vasodilatation in apolipoprotein E\u2010deficient mice (ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>).<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Changes in isometric tension were recorded on a myograph; simultaneously, NO and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> were measured using carbon microsensors. Antisense oligodeoxynucleotides were used to knockdown eNOS and nNOS <jats:italic>in vivo<\/jats:italic>. Western blot and confocal microscopy were used to analyse the expression and localization of NOS isoforms.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Aortas from ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed impaired vasodilatation paralleled by decreased NO and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production. Inhibition of nNOS with L\u2010Arg<jats:sup>NO2<\/jats:sup>\u2010L\u2010Dbu, knockdown of nNOS and catalase, which decomposes H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> into oxygen and water, decreased ACh\u2010induced relaxation by half, produced a small diminution of NO production and abolished H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in wild\u2010type animals, but had no effect in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Confocal microscopy showed increased nNOS immunostaining in endothelial cells of ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice. However, ACh stimulation of vessels resulted in less phosphorylation on Ser852 in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> Our data show that endothelial nNOS\u2010derived H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production is impaired and contributes to endothelial dysfunction in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> aorta. The present study provides a new mechanism for endothelial dysfunction in atherosclerosis and may represent a novel target to elaborate the therapeutic strategy for vascular atherosclerosis.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01500.x","type":"journal-article","created":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T11:53:34Z","timestamp":1306410814000},"page":"1738-1748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Decreased production of neuronal NOS\u2010derived hydrogen peroxide contributes to endothelial dysfunction in atherosclerosis"],"prefix":"10.1111","volume":"164","author":[{"given":"LSA","family":"Capettini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SF","family":"Cortes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JF","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JI","family":"Alvarez\u2010Leite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"VS","family":"Lemos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3570593"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000089601.87125.E4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.07.006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.12.1271"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.30.4.934"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000159147"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.10.840"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00731.2008"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.06.066"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000164093.88821.00"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.11.1230"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015253"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.10.007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000095380.06622.D8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0337-9"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.12.1416"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2010.04.001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)88969-5"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.01.006"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00394.2009"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-08-1102"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00501.2001"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm990111c"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.9.2224"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000121569.76931.0b"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2007.06.1469"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.11.4651"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00546.2002"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000223143.88128.19"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.5.856"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.9.1282"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.09.009"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026493425977"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1932-8737.1997.tb00006.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10506"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6278"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000054200.44505.AB"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0155fje"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.9.2396"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1232-7"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705164"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1061"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(99)70266-8"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.02.033"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0841"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-008-0678-5"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.11.2290"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000139450.64337.cd"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.2.3"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.10.066"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.11.41"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119826"},{"key":"e_1_2_8_54_1","first-page":"213","article-title":"The endothelium and arterial reactivity","volume":"11","author":"Vanhoutte PM","year":"1986","journal-title":"J Mal Vasc"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42315"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(99)00051-4"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.11.2479"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000050145.25589.65"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.34"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2011.01500.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1476-5381.2011.01500.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T04:18:24Z","timestamp":1697429904000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01500.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,24]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["10.1111\/j.1476-5381.2011.01500.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01500.x","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,24]]},"assertion":[{"value":"2011-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}