{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:23:58Z","timestamp":1786123438925,"version":"build-2736575974"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Dexmedetomidine (DEX) has a direct cardioprotective effect against ischemia\/reperfusion injury through endothelial nitric oxide synthase (eNOS) phosphorylation via \u03b12-adrenoreceptor (\u03b12-AR). By using spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models, the cardioprotective effect of DEX in hypertrophied myocardium and the differential characteristics of cardiac \u03b12-AR and the I1 imidazoline receptor (I1R) were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Langendorff-perfused rat hearts underwent 40 minutes of global ischemia followed by 120 minutes of reperfusion in the presence or absence of DEX before ischemia. Infarct size was measured, and eNOS phosphorylation was assessed by Western blotting. The presence and expression of the receptors were assessed by immunohistochemistry, real-time reverse transcriptase polymerase chain reaction, and Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>In WKY, DEX significantly decreased infarct size and increased phosphorylated-eNOS\/eNOS. These effects were counteracted by yohimbine (\u03b12-AR antagonist) and efaroxan (\u03b12-AR and I1R antagonist). In SHR, DEX significantly decreased infarct size, and the effect was counteracted by efaroxan but not yohimbine. DEX did not alter phosphorylated-eNOS\/eNOS in SHR. \u03b12-AR and I1R were observed in WKY and SHR hearts. Although alpha2A-AR and alpha2B-AR messenger RNA and protein levels were upregulated in SHR, I1R expression was comparable between the 2 species.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In the hypertrophied heart, DEX maintains its direct cardioprotective effect against ischemia\/reperfusion injury via I1R in an eNOS-nondependent manner despite upregulation of \u03b12-AR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1213\/ane.0000000000002452","type":"journal-article","created":{"date-parts":[[2017,9,13]],"date-time":"2017-09-13T18:46:04Z","timestamp":1505328364000},"page":"443-452","source":"Crossref","is-referenced-by-count":43,"title":["Dexmedetomidine Maintains Its Direct Cardioprotective Effect Against Ischemia\/Reperfusion Injury in Hypertensive Hypertrophied Myocardium"],"prefix":"10.1213","volume":"126","author":[{"given":"Yusuke","family":"Yoshikawa","sequence":"first","affiliation":[{"name":"From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Hirata","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Tokinaga","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiaki","family":"Yamakage","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230812","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/SHK.0b013e3182a0674b","article-title":"Hypertrophied myocardium is refractory to sevoflurane-induced protection with alteration of reperfusion injury salvage kinase\/glycogen synthase kinase 3\u03b2 signals.","volume":"40","author":"Ma","year":"2013","journal-title":"Shock"},{"key":"R2-20230812","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1161\/HYPERTENSIONAHA.110.158469","article-title":"Hypertensive hypertrophied myocardium is vulnerable to infarction and refractory to erythropoietin-induced 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