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One of the numerous side effects of dexamethasone therapy is hypertension arising from reduced release of the endothelium\u2010derived vasodilator nitric oxide (NO).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Herein, we described the role of dexamethasone and its glucocorticoid receptor (GR) in the regulation of NO synthesis<jats:italic>in vitro<\/jats:italic>using the mouse myocardial microvascular endothelial cell line, MyEND. GC treatment caused a firm decrease of extracellular NO levels, whereas the expression of endothelial NO synthase (eNOS) was not affected. However, GC application induced an impairment of tetrahydrobiopterin (BH<jats:sub>4<\/jats:sub>) concentrations as well as GTP cyclohydrolase\u20101 (GTPCH\u20101) expression, both essential factors for NO production upstream of eNOS. Moreover, dexamethasone stimulation resulted in a substantially decreased<jats:italic>GR<\/jats:italic>gene and protein expression in MyEND cells. Importantly, inhibition of proteasome\u2010mediated proteolysis of the GR or overexpression of an ubiquitination\u2010defective GR construct improved the bioavailability of BH<jats:sub>4<\/jats:sub>and strengthened GTPCH\u20101 expression and eNOS activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Summarising our results, we propose a new mechanism involved in the regulation of NO signalling by GCs in myocardial endothelial cells. We suggest that a sufficient GR protein expression plays a crucial role for the management of GC\u2010induced harmful adverse effects, including deregulations of vasorelaxation arising from disturbed NO biosynthesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/boc.201300083","type":"journal-article","created":{"date-parts":[[2014,4,19]],"date-time":"2014-04-19T10:52:48Z","timestamp":1397904768000},"page":"219-235","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of proteasome\u2010mediated glucocorticoid receptor degradation restores nitric oxide bioavailability in myocardial endothelial cells<i>in vitro<\/i>"],"prefix":"10.1111","volume":"106","author":[{"given":"Kinga G.","family":"Blecharz","sequence":"first","affiliation":[{"name":"University of W\u00fcrzburg Department of Anaesthesia and Critical Care W\u00fcrzburg 97080 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Burek","sequence":"additional","affiliation":[{"name":"University of W\u00fcrzburg Department of Anaesthesia and Critical Care W\u00fcrzburg 97080 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Hannover Medical School Klinik f\u00fcr Kardiologie und Angiologie Hannover 30625 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[{"name":"Hannover Medical School Institute for Molecular and Translational Therapeutic Strategies Hannover 30625 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Tsikas","sequence":"additional","affiliation":[{"name":"Hannover Medical School Department of Clinical Pharmacology Hannover 30625 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Widder","sequence":"additional","affiliation":[{"name":"Hannover Medical School Klinik f\u00fcr Kardiologie und Angiologie Hannover 30625 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Roewer","sequence":"additional","affiliation":[{"name":"University of W\u00fcrzburg Department of Anaesthesia and Critical Care W\u00fcrzburg 97080 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola Y.","family":"F\u00f6rster","sequence":"additional","affiliation":[{"name":"University of W\u00fcrzburg Department of Anaesthesia and Critical Care W\u00fcrzburg 97080 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-004-0046-0"},{"key":"e_1_2_10_3_1","first-page":"H1293","article-title":"Induction of NO synthase in rat cardiac microvascular endothelial cells by IL\u20101 beta and IFN\u2010gamma","volume":"268","author":"Balligand J.L.","year":"1995","journal-title":"Am. 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