{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T10:07:11Z","timestamp":1718964431685},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"10","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:p>Abnormal glucocorticoid metabolism contributes to vascular dysfunction and cardiovascular disease. Cortisol activation of vascular mineralocorticoid and glucocorticoid receptors is regulated by two types of 11\u03b2-HSD (11-\u03b2 hydroxysteroid dehydrogenase), namely 11\u03b2-HSD2 and 11\u03b2-HSD1 (type 2 and type 1 11\u03b2-HSD respectively). We hypothesized that inhibition of 11\u03b2-HSD would attenuate vascular function in healthy humans. A total of 15 healthy subjects were treated with the selective 11\u03b2-HSD inhibitor GA (glycyrrhetinic acid) or matching placebo in a randomized double-blinded cross-over trial. 11\u03b2-HSD activity was assessed by the urinary cortisol\/cortisone ratio, and vascular function was measured using strain-gauge plethysmography. Endothelial function was measured through incremental brachial artery administration of methacholine (0.3\u201310\u00a0\u03bcg\/min) and vascular smooth muscle function with incremental verapamil (10\u2013300\u00a0\u03bcg\/min). GA increased the 24-h urinary cortisol\/cortisone ratio compared with placebo (P=0.008). GA tended to reduce the FBF (forearm blood flow) response to methacholine (P=0.09) and significantly reduced the FBF response to verapamil compared with placebo (P=0.04). MAP (mean arterial pressure) did not differ between the study conditions. 11\u03b2-HSD inhibition attenuated vascular smooth muscle vasodilatory function in healthy humans. Disturbances in cortisol activity resulting from 11\u03b2-HSD inactivation is therefore a second plausible mechanism for mineralocorticoid-mediated hypertension in humans.<\/jats:p>","DOI":"10.1042\/cs20100087","type":"journal-article","created":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T11:38:31Z","timestamp":1275478711000},"page":"437-442","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Glycyrrhetinic acid attenuates vascular smooth muscle vasodilatory function in healthy humans"],"prefix":"10.1042","volume":"119","author":[{"given":"Piotr","family":"Sobieszczyk","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry\u00a0A.","family":"Borlaug","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather\u00a0L.","family":"Gornik","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesley\u00a0D.","family":"Knauft","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua\u00a0A.","family":"Beckman","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2010,8,5]]},"reference":[{"key":"2021113010114271800_B1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/0960-0760(91)90036-5","article-title":"The cortisol-cortisone shuttle and the apparent specificity of glucocorticoid and mineralocorticoid receptors","volume":"39","author":"Edwards","year":"1991","journal-title":"J. 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