{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:56:14Z","timestamp":1794012974938,"version":"4.8.0"},"reference-count":34,"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":[[2003,11]]},"abstract":"<jats:p>\n            Vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species play critical roles in early atherogenesis, and nitric oxide (NO) is an important regulator of the cardiovascular system. Although celiprolol, a specific \u03b2\n            <jats:sub>1<\/jats:sub>\n            -antagonist with weak \u03b2\n            <jats:sub>2<\/jats:sub>\n            -agonistic action, stimulates endothelial nitric oxide synthase (eNOS) production, the mechanisms remain to be determined. Because it was recently reported that phosphatidylinositol 3-kinase (PI3K) and its downstream effector Akt are implicated in the activation of eNOS and that regulation of VCAM-1 expression is mediated via nuclear factor-\u03baB (NF-\u03baB), we hypothesized that celiprolol activates phosphorylation of eNOS through the PI3K-Akt signaling pathway; that celiprolol modulates VCAM-1 expression, which is associated with inhibiting NF-\u03baB phosphorylation; and that celiprolol suppresses NAD(P)H oxidase p22phox, p47phox, gp91phox, and nox1 expression in the left ventricle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. eNOS and Akt phosphorylation upregulated by celiprolol alone were suppressed by treatment with celiprolol plus wortmannin. Increased expression of VCAM-1, p22phox, p47phox, gp91phox, nox1, activated p65 NF-\u03baB, c-Src, p44\/p42 extracellular signal-regulated kinases, and their downstream effector p90 ribosomal S6 kinase phosphorylation in DOCA rats was inhibited by celiprolol. Celiprolol administration resulted in a significant improvement in cardiovascular remodeling and suppression of transforming growth factor-\u03b21 gene expression. In conclusion, celiprolol suppresses VCAM-1 expression because of inhibition of oxidative stress, NF-\u03baB, and signal transduction, while increasing eNOS via stimulation of the PI3K-Akt signaling pathway and improving cardiovascular remodeling.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000097547.35570.70","type":"journal-article","created":{"date-parts":[[2003,10,14]],"date-time":"2003-10-14T00:28:53Z","timestamp":1066091333000},"page":"1004-1013","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":76,"title":["Celiprolol Activates eNOS Through the PI3K-Akt Pathway and Inhibits VCAM-1 Via NF-\u03baB Induced by Oxidative Stress"],"prefix":"10.1161","volume":"42","author":[{"given":"Naohiko","family":"Kobayashi","sequence":"first","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichiro","family":"Mita","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohtaro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeaki","family":"Honda","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Hara","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigefumi","family":"Nakano","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Tsubokou","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"From the Department of Hypertension and Cardiorenal Medicine, Dokkyo 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