{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T21:12:41Z","timestamp":1724965961584},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3348,"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":[[1999,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>PF9404C is the S\u2010S diesteroisomer of a novel blocker of beta adrenergic receptors with vasodilatory properties. It causes a concentration\u2010dependent relaxation of rat aorta helical strips pre\u2010contracted with 10<jats:sup>\u22126<\/jats:sup> <jats:sc>M<\/jats:sc> noradrenaline (NA; IC<jats:sub>50<\/jats:sub> 33\u2003n<jats:sc>M<\/jats:sc>). It was equipotent to nitroglycerin (NTG; IC<jats:sub>50<\/jats:sub> 49\u2003n<jats:sc>M<\/jats:sc>), but much more potent than isosorbide dinitrate (ISD; IC<jats:sub>50<\/jats:sub> 15,000\u2003n<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Oxyhaemoglobin (10\u2003\u03bc<jats:sc>M<\/jats:sc>) shifted to the right the concentration\u2010response curve for the relaxation induced by PF9404C (IC<jats:sub>50<\/jats:sub> 530\u2003n<jats:sc>M<\/jats:sc>) or NTG (IC<jats:sub>50<\/jats:sub> 61\u2003n<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Either methylene blue (MB) or ODQ (1\u2003\u03bc<jats:sc>M<\/jats:sc> each) largely prevented the vasorelaxing responses to increasing concentrations of PF9404C or NTG.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In rat aorta smooth muscle cells, PF9404C increased the formation of cyclic GMP from 3 pmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein in basal conditions, to 53\u2003pmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein in 10\u2003\u03bc<jats:sc>M<\/jats:sc> PF9404C. Neither metoprolol nor carvedilol enhanced cyclic GMP.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the electrically driven guinea\u2010pig left atrium, PF9404C blocked the inotropic effects of isoprenaline in a concentration\u2010dependent manner. Its IC<jats:sub>50<\/jats:sub> (30\u2003n<jats:sc>M<\/jats:sc>) was similar to that for S\u2010propranolol (22.4\u2003n<jats:sc>M<\/jats:sc>) and lower than the IC<jats:sub>50<\/jats:sub>s for metoprolol (120\u2003n<jats:sc>M<\/jats:sc>) and atenolol (192\u2003n<jats:sc>M<\/jats:sc>). The beta\u2010adrenergic ligand (\u2212)\u2010[<jats:sup>3<\/jats:sup>H]\u2010CGP12177 (0.2\u2003n<jats:sc>M<\/jats:sc>) was displaced from its binding to rat brain membranes with <jats:italic>K<jats:sub>i<\/jats:sub><\/jats:italic> of 7\u2003n<jats:sc>M<\/jats:sc>, 17\u2003n<jats:sc>M<\/jats:sc>, 170\u2003n<jats:sc>M<\/jats:sc> and 1.2\u2003\u03bc<jats:sc>M<\/jats:sc> respectively for PF9404C, S\u2010(\u2212)propranolol, metoprolol, and atenolol.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The data are consistent with the idea that the S\u2010S diesteroisomer PF9404C, is a potent vasorelaxing agent, as well as a blocker of cardiac beta adrenergic receptors. The mechanism of its vasorelaxing effects involves the slow generation of NO. This molecule can, therefore, exhibit antihypertensive and cardioprotective actions through a double mechanism, NO donation and beta blockade.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 1713\u20131722; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702992\">10.1038\/sj.bjp.0702992<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702992","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:29:41Z","timestamp":1106944181000},"page":"1713-1722","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PF9404C, a new slow NO donor with beta receptor blocking properties"],"prefix":"10.1111","volume":"128","author":[{"given":"Mercedes","family":"Villarroya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos J","family":"Herrero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Ru\u00edz\u2010Nu\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"De Pascual","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Del Valle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Michelena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Grau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Carrasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela G","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio G","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"184","article-title":"PF9104: a novel beta\u2010blocker with coronary and peripheral vasodilatory properties","volume":"18","author":"ANT\u00d3N F.","year":"1996","journal-title":"Meth. 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