{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T16:32:10Z","timestamp":1794241930843,"version":"4.9.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,11,9]]},"abstract":"<jats:p>\n                    Hypertension is a side effect of systemically administered glucocorticoids, but the underlying molecular mechanism remains poorly understood. Ingestion of dexamethasone by rats telemetrically instrumented increased blood pressure progressively over 7 days. Plasma concentrations of Na\n                    <jats:sup>+<\/jats:sup>\n                    and K\n                    <jats:sup>+<\/jats:sup>\n                    and urinary Na\n                    <jats:sup>+<\/jats:sup>\n                    and K\n                    <jats:sup>+<\/jats:sup>\n                    excretion remained constant, excluding a mineralocorticoid-mediated mechanism. Plasma NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    (the oxidation products of NO) decreased to 40%, and the expression of endothelial NO synthase (NOS III) was found down-regulated in the aorta and several other tissues of glucocorticoid-treated rats. The vasodilator response of resistance arterioles was tested by intravital microscopy in the mouse dorsal skinfold chamber model. Dexamethasone treatment significantly attenuated the relaxation to the endothelium-dependent vasodilator acetylcholine, but not to the endothelium-independent vasodilator S-nitroso-\n                    <jats:italic>N<\/jats:italic>\n                    -acetyl-\n                    <jats:sc>d<\/jats:sc>\n                    ,\n                    <jats:sc>l<\/jats:sc>\n                    -penicillamine. Incubation of human umbilical vein endothelial cells, EA.hy 926 cells, or bovine aortic endothelial cells with several glucocorticoids reduced NOS III mRNA and protein expression to 60\u201370% of control, an effect that was prevented by the glucocorticoid receptor antagonist mifepristone. Glucocorticoids decreased NOS III mRNA stability and reduced the activity of the human NOS III promoter (3.5 kilobases) to \u224870% by decreasing the binding activity of the essential transcription factor GATA. The expressional down-regulation of endothelial NOS III may contribute to the hypertension caused by glucocorticoids.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.23.13357","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"13357-13362","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":245,"title":["Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension"],"prefix":"10.1073","volume":"96","author":[{"given":"Thomas","family":"Wallerath","sequence":"first","affiliation":[{"name":"Departments of Pharmacology, Pathology, and Clinical Chemistry, Johannes Gutenberg University Medical School, 55101 Mainz, Germany; Institute of Pharmacology and Toxicology, Faculty of Clinical Medicine Mannheim, Ruprecht Karls University Heidelberg, 68169 Mannheim, Germany; and Hoechst Marion 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Mannheim, Germany; and Hoechst Marion Roussel (HMR), Disease Group Cardiovascular Agents, 65926 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra M.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Pathology, and Clinical Chemistry, Johannes Gutenberg University Medical School, 55101 Mainz, Germany; Institute of Pharmacology and Toxicology, Faculty of Clinical Medicine Mannheim, Ruprecht Karls University Heidelberg, 68169 Mannheim, Germany; and Hoechst Marion Roussel (HMR), Disease Group Cardiovascular Agents, 65926 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Prellwitz","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Pathology, and Clinical Chemistry, Johannes Gutenberg University Medical School, 55101 Mainz, Germany; Institute of Pharmacology and Toxicology, Faculty of Clinical Medicine Mannheim, Ruprecht Karls 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