{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:15:36Z","timestamp":1790867736296,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3591,"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":[[1999,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Some animal studies suggest that \u03b2\u2010adrenoceptor\u2010mediated vasorelaxation is in part mediated through nitric oxide (NO) release. Furthermore, in humans, we have recently shown that forearm blood flow is increased by infusion of \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic agonists into the brachial artery, and the nitric oxide synthase (NOS) inhibitor N<jats:sup>G<\/jats:sup>\u2010monomethyl\u2010<jats:sc>L<\/jats:sc>\u2010arginine (<jats:sc>L<\/jats:sc>\u2010NMMA) inhibits this response.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The purpose of the present study was to determine whether stimulation of human umbilical vein endothelial \u03b2\u2010adrenoceptors causes vasorelaxation and nitric oxide generation, and whether this might be mediated by cyclic adenosine\u20103\u2032,5\u2032\u2010monophosphate (cyclic AMP).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Vasorelaxant responses were determined in umbilical vein rings to the nonselective \u03b2\u2010adrenergic agonist isoprenaline and to the cyclic AMP analogue dibutyryl cyclic AMP, following precontraction with prostaglandin F<jats:sub>2\u03b1<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NOS activity was measured in cultured human umbilical vein endothelial cells (HUVEC) by the conversion of [<jats:sup>3<\/jats:sup>H]\u2010<jats:sc>L<\/jats:sc>\u2010arginine to [<jats:sup>3<\/jats:sup>H]\u2010<jats:sc>L<\/jats:sc>\u2010citrulline, and adenylyl cyclase activity by the conversion of [\u03b1\u2010<jats:sup>32<\/jats:sup>P]\u2010ATP to [<jats:sup>32<\/jats:sup>P]\u2010cyclic AMP.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Isoprenaline relaxed umbilical vein rings, and this vasorelaxation was abolished by \u03b2<jats:sub>2<\/jats:sub>\u2010 (but not \u03b2<jats:sub>1<\/jats:sub>\u2010) adrenergic blockage, and by endothelium removal or 1\u2003m<jats:sc>M<\/jats:sc> <jats:sc>L<\/jats:sc>\u2010NMMA. In addition, vasorelaxant responses to dibutyryl cyclic AMP were inhibited by 1\u2003m<jats:sc>M<\/jats:sc> <jats:sc>L<\/jats:sc>\u2010NMMA, with a reduction in E<jats:sub>max<\/jats:sub> from 90.0\u00b19.3% to 50.5\u00b19.9% (<jats:italic>P<\/jats:italic>&lt;0.05).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Isoprenaline 1\u2003\u03bc<jats:sc>M<\/jats:sc> increased NOS activity in HUVEC (34.0\u00b15.9% above basal, <jats:italic>P<\/jats:italic>&lt;0.001). Furthermore, isoprenaline increased adenylyl cyclase activity in a concentration\u2010dependent manner; this response was inhibited by \u03b2<jats:sub>2<\/jats:sub> (but not \u03b2<jats:sub>1<\/jats:sub>\u2010) adrenergic blockade. Forskolin 1\u2003\u03bc<jats:sc>M<\/jats:sc> and dibutyryl cyclic AMP 1\u2003m<jats:sc>M<\/jats:sc> each increased NOS activity in HUVEC, to a degree similar to isoprenaline 1\u2003\u03bc<jats:sc>M<\/jats:sc>. The increase in <jats:sc>L<\/jats:sc>\u2010arginine to <jats:sc>L<\/jats:sc>\u2010citrulline conversion observed with each agent was abolished by co\u2010incubation with NOS inhibitors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results indicate that endothelial \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic stimulation and cyclic AMP elevation activate the <jats:sc>L<\/jats:sc>\u2010arginine\/NO system, and give rise to vasorelaxation, in human umbilical vein.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 1872\u20131880; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702512\">10.1038\/sj.bjp.0702512<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702512","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:58:52Z","timestamp":1106942332000},"page":"1872-1880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["Activation of nitric oxide synthase by <i>\u03b2<\/i><sub>2<\/sub>\u2010adrenoceptors in human umbilical vein endothelium <i>in vitro<\/i>"],"prefix":"10.1111","volume":"126","author":[{"given":"Albert","family":"Ferro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay R","family":"Queen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M","family":"Priest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Ritter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Poston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P T","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80876-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb14839.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1987.tb11302.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198305000-00013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90178-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb09053.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112779"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(96)00550-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1987.tb11324.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.5.984"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.9.2293"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(92)90710-G"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb09854.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)91518-0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2880345"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0898-6568(90)90067-K"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb12853.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14507.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.65.3.1251"},{"key":"e_1_2_7_21_1","first-page":"890","article-title":"Involvement of endothelial cells in relaxation and contraction responses of the aorta to isoproterenol in naive and streptozotocin\u2010induced diabetic rats","volume":"249","author":"KAMATA K.","year":"1989","journal-title":"J. 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