{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:40:31Z","timestamp":1791520831884,"version":"4.3.4"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Aldosterone\u2010producing adenoma (APA) is a major cause of primary aldosteronism, the most frequent form of secondary hypertension. Although somatic mutations in ion channels within APA have been shown to activate Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling and drive aldosterone production, the pathophysiology of primary aldosteronism remains partially understood. SP (Substance P), encoded by the\n                      <jats:italic toggle=\"no\">TAC1<\/jats:italic>\n                      gene, is a neuropeptide of the tachykinin family, known for its role in stimulating aldosterone production through activation of the neurokinin 1 receptor (NK1R) in the human adrenal cortex. The aim of our work was to investigate the presence of SP nerve fibers and the NK1R in a large series of APA to assess the potential role of tachykinins in the pathophysiology of primary aldosteronism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Using molecular, immunohistochemical, and functional techniques, 56 APA tissues were analyzed to assess the expression of SP and NK1R and their impact on aldosterone secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">SP\u2010positive nerve fibers were detected in 90% of the APA tissues, localized both within and around the adenomas, which also showed strong NK1R expression. Functional studies revealed that SP stimulated aldosterone secretion in 6 of 10 APA cultures. The NK1R antagonist aprepitant inhibited SP\u2010induced aldosterone secretion in 3 of the 4 SP\u2010responsive APA cultures on which the antagonist was tested. Additionally, in perifused APA explants, SP influenced aldosterone pulsatility, resulting in enhanced mineralocorticoid secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">These findings suggest that the SP\u2010NK1R signaling pathway may contribute to APA pathophysiology and represent a novel potential target for the pharmacological treatment of PA in a subset of patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.045539","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:44:36Z","timestamp":1768391076000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Regulation of Aldosterone Secretion by Substance P and the Neurokinin Type 1 Receptor in Aldosterone\u2010Producing Adenomas"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3479-8693","authenticated-orcid":false,"given":"Antoine\u2010Guy","family":"Lopez","sequence":"first","affiliation":[{"name":"Univ Rouen Normandie, Inserm, NorDiC UMR 1239, CHU Rouen","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-6287","authenticated-orcid":false,"given":"C\u00e9line","family":"Duparc","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm, NorDiC UMR 1239","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Renouf","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm, NorDiC UMR 1239","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm, NorDiC UMR 1239","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5011-5530","authenticated-orcid":false,"given":"Kelly","family":"De Sousa","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm, NorDiC UMR 1239","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3942-4276","authenticated-orcid":false,"given":"Laurence","family":"Amar","sequence":"additional","affiliation":[{"name":"H\u00f4pital Europ\u00e9en Georges Pompidou","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Defortescu","sequence":"additional","affiliation":[{"name":"CHU Rouen","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0783-8688","authenticated-orcid":false,"given":"Gilles","family":"Manceau","sequence":"additional","affiliation":[{"name":"Georges Pompidou University Hospital, Paris Cit\u00e9 University","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Christophe","family":"Sabourin","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, CHU Rouen","place":["Rouen, France"]},{"name":"CHU Rouen","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0162-0792","authenticated-orcid":false,"given":"Fabio Luiz","family":"Fernandes\u2010Rosa","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, PARCC, Inserm","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-9191","authenticated-orcid":false,"given":"Maria\u2010Christina","family":"Zennaro","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, PARCC, Inserm","place":["Paris, France"]},{"name":"H\u00f4pital Europ\u00e9en Georges Pompidou, Service de G\u00e9n\u00e9tique","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tchao","family":"Meatchi","sequence":"additional","affiliation":[{"name":"H\u00f4pital Europ\u00e9en Georges Pompidou, Service d\u2019anatomie pathologique","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Nicolas","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, CHU Rouen","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4723-095X","authenticated-orcid":false,"given":"Estelle","family":"Louiset","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm, NorDiC UMR 1239","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-9648","authenticated-orcid":false,"given":"Herv\u00e9","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm, NorDiC UMR 1239, CHU Rouen","place":["Rouen, France"]},{"name":"CHU Rouen","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaf284"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30135-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2016.02.003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa484"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03419"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14177"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198785"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2550"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2716"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2695"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06315"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0048-5"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0053-8"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.125.24909"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt484"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab707"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep39121"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-08-0711"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa703"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.3.8327"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1153374"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.01253.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.644382"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5444.1558"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.91.87"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30823-1"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2013"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16470-8"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050444"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.08.019"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3660"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0931458100"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90047-6"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09746"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0005"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104850"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7148-1"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01835156"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1177\/44.4.8601696"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.052808.102215"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.11.010"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(91)90213-o"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(91)90205-j"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00017.x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1998.tb00227.x"},{"key":"e_1_3_2_47_2","first-page":"120","article-title":"Divergent differentiation in neuroendocrine tumors of the adrenal gland","volume":"17","author":"Tischler AS","year":"2000","unstructured":"Tischler AS. Divergent differentiation in neuroendocrine tumors of the adrenal gland. Semin Diagn Pathol. 2000;17:120\u2013126.","journal-title":"Semin Diagn Pathol"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1243"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1243602"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(24)00200-6"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00174-06"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/495704"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0165-6147(97)01107-3"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.80.1.7829626"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.07.002"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2015-1080"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135821"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.19.2.0326"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.09.009"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(88)90102-7"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.045539","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:12:28Z","timestamp":1782990748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.045539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,1,20]]}},"alternative-id":["10.1161\/JAHA.125.045539"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.045539","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]},"assertion":[{"value":"2025-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e045539"}}