{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:46:40Z","timestamp":1790063200885,"version":"4.0.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2013,10,12]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Overactivity of the brain renin\u2013angiotensin system is a major contributor to neurogenic hypertension. Although overexpression of angiotensin-converting enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming angiotensin II into angiotensin-(1\u20137), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>To test this hypothesis, we used the deoxycorticosterone acetate\u2013salt model of neurogenic hypertension in nontransgenic and syn-hACE2 mice overexpressing ACE2 in neurons. Deoxycorticosterone acetate\u2013salt treatment in nontransgenic mice led to significant increases in blood pressure, hypothalamic angiotensin II levels, inflammation, impaired baroreflex sensitivity, and autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, although these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled an increase in ACE2 activity in the cerebrospinal fluid of nontransgenic mice after deoxycorticosterone acetate\u2013salt treatment and were accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.113.301811","type":"journal-article","created":{"date-parts":[[2013,9,7]],"date-time":"2013-09-07T05:38:56Z","timestamp":1378532336000},"page":"1087-1096","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":160,"title":["Brain Angiotensin-Converting Enzyme Type 2 Shedding Contributes to the Development of Neurogenic Hypertension"],"prefix":"10.1161","volume":"113","author":[{"given":"Huijing","family":"Xia","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Experimental Therapeutics and Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Sriramula","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Experimental Therapeutics and Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavaljit H.","family":"Chhabra","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Experimental Therapeutics and Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lazartigues","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Experimental Therapeutics and Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00222.2010"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2013.01.010"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-008-0668-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3283406f57"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.113.301271"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00292.2006"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.208645"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.108.123844"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr242"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.111.176636"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000259942.38108.20"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505111200"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000135483.12297.e4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2013.01.003"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.12.2.214"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-010-0105-7"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02741376"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.217299"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.139"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.11.085"},{"key":"e_1_3_4_22_2","first-page":"H261","article-title":"Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats.","volume":"251","author":"Itaya Y","year":"1986","unstructured":"Itaya Y, Suzuki H, Matsukawa S, Kondo K, Saruta T. Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats. Am J Physiol. 1986;251:H261\u2013H268.","journal-title":"Am J Physiol"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.23.109"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2001.16.5.553"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/1056-8719(92)90036-Z"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.110.165829"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2008.046334"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00584856"},{"key":"e_1_3_4_29_2","first-page":"H167","article-title":"Evidence that centrally released arginine vasopressin is involved in central pressor action of angiotensin II.","volume":"270","author":"Lo\u0144 S","year":"1996","unstructured":"Lo\u0144 S, Szczepa\u0144ska-Sadowska E, Szczypaczewska M. Evidence that centrally released arginine vasopressin is involved in central pressor action of angiotensin II. Am J Physiol. 1996;270:H167\u2013H173.","journal-title":"Am J Physiol"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.10.1047"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.11.4095"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1179\/174313208X353677"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.110.150409"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200405000-00024"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00376.2002"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00012.2009"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-009-9676-2"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000236203.90331.d0"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.12.009"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502906200"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08-12-1256"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.365171"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.05.005"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi200525y"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00071.2009"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00183.2008"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00036.2009"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2004.05.003"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037649"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.108.127670"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.207415"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.113.301811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:34:01Z","timestamp":1715571241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.113.301811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,12]]},"references-count":50,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,10,12]]}},"alternative-id":["10.1161\/CIRCRESAHA.113.301811"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.113.301811","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,12]]},"assertion":[{"value":"2013-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}