{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T01:03:36Z","timestamp":1785805416621,"version":"3.56.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2016,4,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>\n                      The hypertensive syndrome of Apparent Mineralocorticoid Excess is caused by loss-of-function mutations in the gene encoding 11\u03b2-hydroxysteroid dehydrogenase type 2 (11\u03b2HSD2), allowing inappropriate activation of the mineralocorticoid receptor by endogenous glucocorticoid. Hypertension is attributed to sodium retention in the distal nephron, but 11\u03b2HSD2 is also expressed in the brain. However, the central contribution to Apparent Mineralocorticoid Excess and other hypertensive states is often overlooked and is unresolved. We therefore used a Cre-Lox strategy to generate 11\u03b2HSD2 brain-specific knockout (\n                      <jats:italic>Hsd11b2<\/jats:italic>\n                      .BKO) mice, measuring blood pressure and salt appetite in adults.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Basal blood pressure, electrolytes, and circulating corticosteroids were unaffected in\n                      <jats:italic>Hsd11b2<\/jats:italic>\n                      .BKO mice. When offered saline to drink,\n                      <jats:italic>Hsd11b2<\/jats:italic>\n                      .BKO mice consumed 3 times more sodium than controls and became hypertensive. Salt appetite was inhibited by spironolactone. Control mice fed the same daily sodium intake remained normotensive, showing the intrinsic salt resistance of the background strain. Dexamethasone suppressed endogenous glucocorticoid and abolished the salt-induced blood pressure differential between genotypes. Salt sensitivity in\n                      <jats:italic>Hsd11b2<\/jats:italic>\n                      .BKO mice was not caused by impaired renal sodium excretion or volume expansion; pressor responses to phenylephrine were enhanced and baroreflexes impaired in these animals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Reduced 11\u03b2HSD2 activity in the brain does not intrinsically cause hypertension, but it promotes a hunger for salt and a transition from salt resistance to salt sensitivity. Our data suggest that 11\u03b2HSD2-positive neurons integrate salt appetite and the blood pressure response to dietary sodium through a mineralocorticoid receptor\u2013dependent pathway. Therefore, central mineralocorticoid receptor antagonism could increase compliance to low-sodium regimens and help blood pressure management in cardiovascular disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.115.019341","type":"journal-article","created":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T23:08:27Z","timestamp":1457392107000},"page":"1360-1370","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["Conditional Deletion of\n                    <i>Hsd11b2<\/i>\n                    in the Brain Causes Salt Appetite and Hypertension"],"prefix":"10.1161","volume":"133","author":[{"given":"Louise C.","family":"Evans","sequence":"first","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Ivy","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Wyrwoll","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"McNairn","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert I.","family":"Menzies","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorbj\u00f8rn H.","family":"Christensen","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emad A.S.","family":"Al-Dujaili","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Kenyon","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Mullins","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Seckl","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Holmes","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Bailey","sequence":"additional","affiliation":[{"name":"From British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2015.01.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2005.02.011"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-70-1-200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8140com"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2005.02.020"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113592"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199401203300305"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199812103392414"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.271676"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4445"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007040401"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013060634"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.163782"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.196410"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb02744.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2013.13"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2012"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3115-05.2006"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1159\/000227807"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.09.037"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-2-819"},{"issue":"6","key":"e_1_3_3_23_2","first-page":"E1125","article-title":"Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone.","volume":"263","author":"Gomez-Sanchez EP","year":"1992","unstructured":"Gomez-Sanchez EP, Gomez-Sanchez CE. Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Am J Physiol. 1992;263(6 Pt 1):E1125\u2013E1130.","journal-title":"Am J Physiol"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2015.05.003"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00165.2012"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.134973"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2008.12.012"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2009.06.009"},{"key":"e_1_3_3_29_2","first-page":"305","article-title":"Methods for cosinor-rhythmometry.","volume":"6","author":"Nelson W","year":"1979","unstructured":"Nelson W, Tong YL, Lee JK, Halberg F. Methods for cosinor-rhythmometry. Chronobiologia. 1979;6:305\u2013323.","journal-title":"Chronobiologia"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2013-0235"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(73)90232-X"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1770"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.5.H2241"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.3.583"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00437.2010"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2011.01.001"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/hbeh.1993.1018"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000035"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-198806000-00002"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0439"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00441.2004"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(95)00140-N"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.5.1201"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.188995"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2012.174"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.193045"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.175"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00622.2006"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.11.3206"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3283015e5a"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.115.019341","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:01:20Z","timestamp":1715569280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.115.019341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,5]]},"references-count":49,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2016,4,5]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.115.019341"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.115.019341","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726204807.793523728","asserted-by":"object"}]},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,5]]},"assertion":[{"value":"2015-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}