{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:47:00Z","timestamp":1769158020342,"version":"3.49.0"},"reference-count":42,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"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":[[2014]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background and Aims:&lt;\/i&gt;&lt;\/b&gt; Cardioprotective effects induced by delayed ischemic preconditioning and by nicorandil are mediated via expression of cardioprotective factors such as COX-2. The present study was undertaken to evaluate whether nicorandil could induce COX-2 in rats and to elucidate its mode of induction pharmacologically. &lt;b&gt;&lt;i&gt;Methods and Results:&lt;\/i&gt;&lt;\/b&gt; Three hours after administration of nicorandil (10 mg\/kg, p.o.), COX-2 mRNA and protein were significantly increased in the left ventricle, although other cardioprotective factors (Bcl-2, eNOS, hexokinase, HSP, and iNOS) were not increased. This COX-2 induction in the left ventricle was preceded by induction of GATA-4, which was significant from 1 h after administration. Ventricular levels of 6-keto-prostaglandin F&lt;sub&gt;1\u03b1&lt;\/sub&gt; were increased 6 h after administration. Although pinacidil or isosorbide dinitrate alone did not increase COX-2 mRNA, their combined application significantly increased COX-2 mRNA. Moreover, although glibenclamide or ODQ each partly inhibited the induction of COX-2 mRNA by nicorandil, their combined application significantly inhibited it. These results suggest that nicorandil induces COX-2 protein through both the activation of K&lt;sub&gt;ATP&lt;\/sub&gt; channels and guanylate cyclase. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; The present study demonstrated that nicorandil induces COX-2 via GATA-4 induction in the heart through both K&lt;sub&gt;ATP&lt;\/sub&gt; channel activation and its nitrate-like properties.<\/jats:p>","DOI":"10.1159\/000360008","type":"journal-article","created":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T08:19:20Z","timestamp":1394698760000},"page":"129-136","source":"Crossref","is-referenced-by-count":3,"title":["GATA-4 Transcription Factor Regulates Cardiac COX-2 Expression Induced by Nicorandil in Left Ventricle of 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