{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:40:08Z","timestamp":1745430008441,"version":"3.40.4"},"reference-count":0,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T00:00:00Z","timestamp":1475020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T00:00:00Z","timestamp":1475020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background and Aims:&lt;\/i&gt;&lt;\/b&gt; Carvedilol ((+\/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), a \u03b2-adrenoceptor-blocker, has multi-channel blocking and vasodilator properties. This agent dose-dependently improves left ventricular function and reduces mortality in patients with arrhythmia and chronic heart failure. However, the effect of carvedilol on the cardiac Na&lt;sup&gt;+&lt;\/sup&gt;\/Ca&lt;sup&gt;2+&lt;\/sup&gt; exchanger (NCX1) has not been investigated. &lt;b&gt;&lt;i&gt;Methods and Results:&lt;\/i&gt;&lt;\/b&gt; We examined the effects of carvedilol and metoprolol, 2 \u03b2-blockers, on Na&lt;sup&gt;+&lt;\/sup&gt;\/Ca&lt;sup&gt;2+&lt;\/sup&gt; exchange current (I&lt;sub&gt;NCX&lt;\/sub&gt;) in guinea-pig cardiac ventricular cells and fibroblasts expressing dog cardiac NCX1. Carvedilol suppressed I&lt;sub&gt;NCX&lt;\/sub&gt; in a concentration-dependent manner but metoprolol did not. IC&lt;sub&gt;50&lt;\/sub&gt; values for the Ca&lt;sup&gt;2+&lt;\/sup&gt; influx (outward) and efflux (inward) components of I&lt;sub&gt;NCX&lt;\/sub&gt; were 69.7 and 61.5 \u00b5mol\/l, respectively. Carvedilol at 100 \u03bcmol\/l inhibited I&lt;sub&gt;NCX&lt;\/sub&gt; in CCL39 cells expressing wild type NCX1 similar to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 \u00b5mol\/l abolished ouabain-induced delayed afterdepolarizations. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Carvedilol inhibited cardiac NCX in a concentration-dependent manner in isolated cardiac ventricles, but metoprolol did not. We conclude that carvedilol inhibits NCX1 at supratherapeutic concentrations.<\/jats:p>","DOI":"10.1159\/000450753","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T21:13:23Z","timestamp":1475010803000},"page":"40-47","source":"Crossref","is-referenced-by-count":4,"title":["Suppressive Effect of Carvedilol on Na&lt;sup&gt;+&lt;\/sup&gt;\/Ca&lt;sup&gt;2+&lt;\/sup&gt; Exchange Current in Isolated Guinea-Pig Cardiac Ventricular Myocytes"],"prefix":"10.1159","volume":"99","author":[{"given":"Miyuki","family":"Tashiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhide","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Yamakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanna","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satomi","family":"Kita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2016,9,28]]},"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/450753","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/450753","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/450753","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:15:38Z","timestamp":1745428538000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000450753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,28]]},"references-count":0,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2017,1,25]]},"published-print":{"date-parts":[[2017,1,31]]}},"URL":"https:\/\/doi.org\/10.1159\/000450753","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"type":"print","value":"0031-7012"},{"type":"electronic","value":"1423-0313"}],"subject":[],"published":{"date-parts":[[2016,9,28]]}}}