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The aim of this study was to evaluate the potential mechanism by which s\u2010Lim exerts its antiarrhythmic effect, focusing on the blockade of \u03b2\u2010adrenoceptor (\u03b2\u2010AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the \u03b2\u2010adrenergic pathway, sarcomeric shortening and L\u2010type calcium current (I<jats:sub>Ca,L<\/jats:sub>). In isolated hearts, 10\u2009\u03bcM of s\u2010Lim did not alter the ECG profile or LVPD. s\u2010Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50\u2009\u03bcM and reduced heart rate at the concentrations of 30 (12.4%) and 50\u2009\u03bcM (16.6%). s\u2010Lim (10\u2009\u03bcM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1\u2009\u03bcM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s\u2010Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker \u03b21\u2010AR). In vivo, s\u2010Lim antagonized the effect of ISO (agonists \u03b21\u2010AR), presenting a similar effect to propranolol (a non\u2010selective blocker \u03b2\u2010AR). In ventricular cardiomyocyte, s\u2010Lim did not alter the voltage dependence for I<jats:sub>Ca,L<\/jats:sub> activation or the I<jats:sub>Ca,L<\/jats:sub> density. In addition, s\u2010Lim did not affect changes in the ECG effect mediated by 5\u2009\u03bcM forskolin (an activator of adenylate cyclase). In an in vivo caffeine\/ISO\u2010induced arrhythmia model, s\u2010Lim (1\u2009mg\/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s\u2010Lim is related to blockade of \u03b2\u2010AR in the heart.<\/jats:p>","DOI":"10.1111\/1440-1681.13915","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T23:12:20Z","timestamp":1725405140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["\u03b2\u2010Adrenergic receptor signalling pathway mediated antiarrhythmic activity of s\u2010limonene in the rat heart"],"prefix":"10.1111","volume":"51","author":[{"given":"Joyce Francielle Ferreira","family":"Santos","sequence":"first","affiliation":[{"name":"Department of Physiology Federal University of Sergipe  Sao Cristovao Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Santos","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Physiology Federal University of Sergipe  Sao Cristovao 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