{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T04:35:40Z","timestamp":1767414940958},"reference-count":64,"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":2009,"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":[[2003,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>Blockers of the rapid component of the delayed rectifier potassium current (<jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>) prolong cardiac action potential duration (APD) and effective refractory period (ERP) in a reverse rate\u2010dependent manner. Since activation of <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptors attenuates prolongation of APD evoked by <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> blockers, rate\u2010dependent neuronal noradrenaline liberation in the myocardium may contribute to the reverse rate\u2010dependent nature of the effects of <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> blockers. In order to test this hypothesis, we studied the effects of dofetilide, a pure <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> blocker, on ERP after activation or blockade of <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptors and after catecholamine depletion in guinea\u2010pig left atrial myocardium paced at 3, 2 and 1 Hz, <jats:italic>in vitro<\/jats:italic>.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Dofetilide (100 n<jats:sc>M<\/jats:sc>) lengthened ERP in a reverse rate\u2010dependent manner in the left atrial myocardium of guinea\u2010pigs. Strong activation of <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptors using 10 n<jats:sc>M<\/jats:sc> isoproterenol abolished the dofetilide\u2010induced lengthening of ERP at all pacing rates.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Blockade of the <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptors with metoprolol (1 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>), atenolol (3 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) or propranolol (300 n<jats:sc>M<\/jats:sc>) increased the dofetilide\u2010evoked prolongation of ERP at 3 and 2 Hz, but not at 1 Hz. As a consequence, metoprolol attenuated while propranolol and atenolol fully eliminated the reverse rate\u2010dependent nature of the dofetilide\u2010induced ERP lengthening. In catecholamine\u2010depleted atrial preparations of the guinea\u2010pig (24 h pretreatment with 5 mg kg<jats:sup>\u22121<\/jats:sup> reserpine i.p.), the effect of dofetilide on ERP was not frequency dependent, and propranolol did not alter the effects of dofetilide.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>In contrast to results obtained in guinea\u2010pig atrial preparations, propranolol failed to change the reverse rate\u2010dependent effect of dofetilide on ERP in the right ventricular papillary muscles of rabbits and guinea\u2010pigs.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>As an indication of the functional consequences of rate\u2010dependent noradrenaline liberation, propranolol decreased twitch tension at 3 and 2 Hz but not at 1 Hz in the atrial myocardium of control guinea\u2010pigs, whereas no such effect was detected in catecholamine\u2010depleted atrial preparations. Propranolol failed to change contractility of ventricular myocardium in guinea\u2010pigs and rabbits.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>It is concluded that rate\u2010dependent noradrenaline release and the ensuing <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptor activation contributed to the reverse rate\u2010dependent nature of ERP prolongation caused by <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> blockers in isolated guinea\u2010pig atrial myocardium.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>139<\/jats:bold>, 1555\u20131563. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705395\">10.1038\/sj.bjp.0705395<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705395","type":"journal-article","created":{"date-parts":[[2003,8,15]],"date-time":"2003-08-15T15:44:23Z","timestamp":1060962263000},"page":"1555-1563","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>\u03b2<\/i>\u2010adrenoceptor activation plays a role in the reverse rate\u2010dependency of effective refractory period lengthening by dofetilide in the guinea\u2010pig atrium, <i>in vitro<\/i>"],"prefix":"10.1111","volume":"139","author":[{"given":"Anik\u00f3","family":"Kov\u00e1cs","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Magyar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"B\u00e1ny\u00e1sz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter P","family":"N\u00e1n\u00e1si","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"Sz\u00e9n\u00e1si","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":"135","article-title":"Differential atrial versus ventricular activities of class III potassium channel blockers","volume":"285","author":"BASKIN E.P.","year":"1998","journal-title":"J. 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