{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:06:43Z","timestamp":1791176803462,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,12,4]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:bold>\n                          <jats:italic>Background<\/jats:italic>\n                        <\/jats:bold>\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    11\u03b2-Hydroxysteroid dehydrogenase (11\u03b2HSD) isozymes catalyze the interconversion of active and inactive glucocorticoids, allowing local regulation of corticosteroid receptor activation. Both are present in the vessel wall; here, using mice with selective inactivation of 11\u03b2HSD isozymes, we test the hypothesis that 11\u03b2HSDs influence vascular function.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:bold>\n                          <jats:italic>Methods and Results<\/jats:italic>\n                        <\/jats:bold>\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    Thoracic aortas were obtained from weight-matched male wild-type (MF1\u00d7129 cross\n                    <jats:sup>+\/+<\/jats:sup>\n                    ), 11\u03b2HSD1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , and 11\u03b2HSD2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. mRNA for both isozymes was detected in wild-type aortas by RT-PCR. 11\u03b2HSD activity in aortic homogenates (48.81\u00b14.65% conversion) was reduced in both 11\u03b2HSD1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    (6.36\u00b12.47% conversion;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.0002) and 11\u03b2HSD2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    (24.71\u00b13.69;\n                    <jats:italic>P<\/jats:italic>\n                    =0.002) mice. Functional responses were unaffected in aortic rings isolated from 11\u03b2HSD1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In contrast, aortas from 11\u03b2HSD2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice demonstrated selectively enhanced constriction to norepinephrine (E\n                    <jats:sub>max<\/jats:sub>\n                    4.28\u00b10.56 versus 1.72\u00b10.47 mN\/mm;\n                    <jats:italic>P<\/jats:italic>\n                    =0.004) attributable to impaired endothelium-derived nitric oxide activity. Relaxation responses to endothelium-dependent and -independent vasodilators were also impaired. To control for chronic renal mineralocorticoid excess, MF1 mice were treated with fludrocortisone (16 weeks) but did not reproduce the functional changes observed in 11\u03b2HSD2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:bold>\n                          <jats:italic>Conclusions<\/jats:italic>\n                        <\/jats:bold>\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    Although both 11\u03b2HSD isozymes are present in the vascular wall, reactivation of glucocorticoids by 11\u03b2HSD1 does not influence aortic function. Mice with 11\u03b2HSD2 knockout, however, have endothelial dysfunction causing enhanced norepinephrine-mediated contraction. This appears to be independent of renal sodium retention and may contribute to hypertension in 11\u03b2HSD2 deficiency.\n                  <\/jats:p>","DOI":"10.1161\/hc4801.100077","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T14:31:09Z","timestamp":1190989869000},"page":"2832-2837","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Endothelial Cell Dysfunction in Mice After Transgenic Knockout of Type 2, but Not Type 1, 11\u03b2-Hydroxysteroid Dehydrogenase"],"prefix":"10.1161","volume":"104","author":[{"given":"Patrick W.F.","family":"Hadoke","sequence":"first","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Christy","sequence":"additional","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri V.","family":"Kotelevtsev","sequence":"additional","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent C.","family":"Williams","sequence":"additional","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Kenyon","sequence":"additional","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Seckl","sequence":"additional","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Mullins","sequence":"additional","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Walker","sequence":"additional","affiliation":[{"name":"From the Endocrinology (P.W.F.H., C.C., B.C.W., C.J.K., J.R.S., B.R.W.), Endothelial Cell Biology (Y.V.K.), and Molecular Physiology (J.J.M.) groups, University of Edinburgh, Edinburgh, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90030-2"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47142-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47248-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.4.8114"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14924"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-129-6-3305"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb02776.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.31.1.459"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00230-2"},{"key":"e_1_3_2_10_2","first-page":"33","volume":"12","year":"1994","unstructured":"Walker BR, Sang KS, Williams BC, et al. Direct and indirect effects of carbenoxolone on responses to glucocorticoids and noradrenaline in rat aorta. J Hypertens. 1994; 12: 33\u201339.","journal-title":"J Hypertens"},{"key":"e_1_3_2_11_2","first-page":"207","volume":"60","year":"1997","unstructured":"Brem AS, Bina RB, Hill N, et al. Effects of licorice derivatives on vascular smooth muscle function. Life Sci. 1997; 60: 207\u2013214.","journal-title":"Life Sci"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92633-S"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0830171"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.27.6.1346"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4445"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600620215"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02512487"},{"key":"e_1_3_2_18_2","first-page":"970","volume":"131","year":"1992","unstructured":"Walker BR, Campbell JC, Williams BC, et al. Tissue-specific distribution of the NAD+-dependent isoform of 11\u03b2-hydroxysteroid dehydrogenase. Endocrinology. 1992; 131: 970\u2013972.","journal-title":"Endocrinology"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(94)00159-J"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.35.5.1099"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.103.25.3129"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.12.4.420"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.20.3.304"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.1.7887"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(00)01201-2"},{"key":"e_1_3_2_26_2","first-page":"13357","volume":"92","year":"1999","unstructured":"Wallerath T, Witte K, Schafer SC, et al. Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci U S A. 1999; 92: 13357\u201313362.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90527-8"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.9.2.157"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.23.5.577"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(95)00118-A"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1993.tb01778.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.27.2.190"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/hc4801.100077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T22:16:30Z","timestamp":1715638590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/hc4801.100077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12,4]]},"references-count":32,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2001,12,4]]}},"alternative-id":["10.1161\/hc4801.100077"],"URL":"https:\/\/doi.org\/10.1161\/hc4801.100077","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,12,4]]},"assertion":[{"value":"2001-12-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}