{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:26:45Z","timestamp":1790987205709,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2000,5]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014This study was designed  to test the hypothesis that stimulation of nicotinamide adenine  dinucleotide\/nicotinamide adenine dinucleotide  phosphate (NADH\/NADPH) oxidase is involved in increased vascular  superoxide anion (\u00b7O\n            <jats:sub>2<\/jats:sub>\n            <jats:sup>\u2212<\/jats:sup>\n            ) production  in spontaneously hypertensive rats (SHR). The study was performed in  16-week-old and 30-week-old normotensive Wistar-Kyoto rats  (WKY\n            <jats:sub>16<\/jats:sub>\n            and WKY\n            <jats:sub>30<\/jats:sub>\n            , respectively) and in  16-week-old and 30-week-old SHR (SHR\n            <jats:sub>16<\/jats:sub>\n            and  SHR\n            <jats:sub>30<\/jats:sub>\n            , respectively). In addition, 16-week-old SHR were  treated with oral irbesartan (average dose 20 mg\/kg per day) for 14  weeks (SHR\n            <jats:sub>30<\/jats:sub>\n            -I). Aortic NADH\/NADPH oxidase activity was  determined by use of chemiluminescence with lucigenin. The expression  of\n            <jats:italic>p22phox<\/jats:italic>\n            messenger RNA was assessed by competitive  reverse transcription\u2013polymerase chain reaction. Vascular responses to  acetylcholine were determined by isometric tension studies. Aortic wall  structure was studied, determining the media thickness and the  cross-sectional area by morphometric analysis. Whereas  systolic blood pressure was significantly increased in the 2  groups of hypertensive animals compared with their normotensive  controls, no differences were observed in systolic blood  pressure between SHR\n            <jats:sub>30<\/jats:sub>\n            and SHR\n            <jats:sub>16<\/jats:sub>\n            . No other  differences in the parameters measured were found between  WKY\n            <jats:sub>16<\/jats:sub>\n            and SHR\n            <jats:sub>16<\/jats:sub>\n            . In SHR\n            <jats:sub>30<\/jats:sub>\n            compared  with WKY\n            <jats:sub>30<\/jats:sub>\n            , we found significantly greater\n            <jats:italic>p22phox<\/jats:italic>\n            mRNA level, NADH\/NADPH-driven  \u00b7O\n            <jats:sub>2<\/jats:sub>\n            <jats:sup>\u2212<\/jats:sup>\n            production, media  thickness, and cross-sectional area and an impaired vasodilation in  response to acetylcholine. Treated SHR had similar NADH\/NADPH oxidase  activity and\n            <jats:italic>p22phox<\/jats:italic>\n            expression as the WKY\n            <jats:sub>30<\/jats:sub>\n            group. The vascular functional and morphological parameters  were improved in SHR\n            <jats:sub>30<\/jats:sub>\n            -I. These findings suggest that an  association exists between\n            <jats:italic>p22phox<\/jats:italic>\n            gene overexpression  and NADH\/NADPH overactivity in the aortas of adult SHR. Enhanced  NADH\/NADPH oxidase\u2013dependent \u00b7O\n            <jats:sub>2<\/jats:sub>\n            <jats:sup>\u2212<\/jats:sup>\n            production may contribute to endothelial  dysfunction and vascular hypertrophy in this genetic model  of hypertension.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.35.5.1055","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"1055-1061","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":279,"title":["Vascular NADH\/NADPH Oxidase Is Involved in Enhanced Superoxide Production in Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"35","author":[{"given":"Guillermo","family":"Zalba","sequence":"first","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of  Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Beaumont","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of  Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorka San","family":"Jose\u0301","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of  Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fortun\u0303o","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of  Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u0301a A.","family":"Fortun\u0303o","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of  Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Etayo","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of  Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Di\u0301ez","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of  Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.4.934"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.5.1083"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.15.2.170"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI650"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.6.1353"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.22.10045"},{"key":"e_1_3_2_7_2","first-page":"366","volume":"21","year":"1996","unstructured":"Miyamoto Y, Akaike T, Yoshida M, Goto S, Horie H, Maeda H. 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