{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:06:14Z","timestamp":1790892374096,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T00:00:00Z","timestamp":1153180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>Nebivolol (NEB) has been shown to be a selective blocker of \u03b2<jats:sub>1<\/jats:sub>\u2010adrenoceptors with additional vasodilating properties that are mediated, at least in part, by an endothelial\u2010dependent liberation of nitric oxide (NO). In the present study, we investigated the underlying mechanisms of NEB\u2010induced vasodilation.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Immunohistochemical staining of endothelial nitric oxide synthase (eNOS) was performed in the absence and presence of NEB in human umbilical vein endothelial cells (HUVEC). In addition, we measured the release of nitric oxide (NO) using diaminofluorescein. Metoprolol (MET) was used for comparison.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Nebivolol, but not MET (each at 10\u00a0\u00b5mol\/L), caused a time\u2010dependent increase in NO release from HUVEC, as demonstrated by an increase in DAF fluorescence at 0 versus 10\u00a0min (+234\u00a0\u00b1\u00a07 and 55\u00a0\u00b1\u00a022% basal, respectively). Blockade of \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptors by SR\u00a059230A (1\u00a0\u00b5mol\/L) partially reduced the NEB\u2010induced increase in DAF fluorescence. Complete inhibition of NEB\u2010induced NO liberation was achieved by the simultaneous blockade of \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptors and oestrogen receptors (with 1\u00a0\u00b5mol\/L ICI\u00a0182,780).<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Application of NEB significantly increased eNOS translocation and serine 1177 phosphorylation of eNOS. However, NEB did not alter eNOS\u2010phosphorylation at threonine 495 and at serine 114.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In conclusion, the endothelium\u2010dependent NO liberation induced by NEB is due to stimulation of \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptors and oestrogen receptors and coincides with eNOS translocation and a phosphorylation at eNOS\u2010serine 1177. These characteristics of NEB may be beneficial not only when treating patients suffering from cardiovascular disease, but may also prevent further deterioration of endothelial dysfunction.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p>","DOI":"10.1111\/j.1440-1681.2006.04424.x","type":"journal-article","created":{"date-parts":[[2010,9,13]],"date-time":"2010-09-13T15:55:39Z","timestamp":1284393339000},"page":"720-724","source":"Crossref","is-referenced-by-count":44,"title":["MECHANISMS UNDERLYING NEBIVOLOL\u2010INDUCED ENDOTHELIAL NITRIC OXIDE SYNTHASE ACTIVATION IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS"],"prefix":"10.1111","volume":"33","author":[{"given":"Dennis","family":"Ladage","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Brixius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Hoyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Steingen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wesseling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Malan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Bloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert HG","family":"Schwinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,18]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704188"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199106000-00016"},{"key":"e_1_2_6_4_2","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0022-3565(25)10549-1","article-title":"Nebivolol vasodilates human forearm vasculature: Evidence for an l\u2010arginine\/NO\u2010dependent mechanism","volume":"274","author":"Cockcroft JR","year":"1995","journal-title":"J. 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