{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:27:15Z","timestamp":1791923235228,"version":"4.3.4"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM144834"],"award-info":[{"award-number":["GM144834"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM088021"],"award-info":[{"award-number":["GM088021"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM075149"],"award-info":[{"award-number":["GM075149"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18TPA34110281"],"award-info":[{"award-number":["18TPA34110281"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24PRE1196925"],"award-info":[{"award-number":["24PRE1196925"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL111084"],"award-info":[{"award-number":["HL111084"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL145836"],"award-info":[{"award-number":["HL145836"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL007736"],"award-info":[{"award-number":["HL007736"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL170503"],"award-info":[{"award-number":["HL170503"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Acid\u2010sensing ion channel 1a (ASIC1a) is a proton\u2010gated cation channel activated by extracellular acidosis, a condition often associated with ischaemia, inflammation and metabolic stress. Our laboratory has previously demonstrated that ASIC1a contributes to systemic endothelium\u2010dependent vasodilatation; however, the role of ASIC1a in blood pressure regulation remains unclear. The objective of this study was to investigate the role of ASIC1a in blood pressure regulation using a model of angiotensin II\u2010induced hypertension. We further determined the effects of age and sex, as these are non\u2010modifiable risk factors for hypertension. Radiotelemeters were implanted in 6\u2010 and 18\u2010month\u2010old male and female wild\u2010type (\n                      <jats:italic>Asic1a<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      ) and ASIC1a knockout (\n                      <jats:italic>Asic1a<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice to continuously measure blood pressure and heart rate under baseline conditions and following angiotensin II. Blood gases, electrolytes, hormones and indices of end\u2010organ injury were also assessed. Deletion of ASIC1 did not significantly alter blood pressure in 6\u2010month\u2010old male or female mice. However, aged male\n                      <jats:italic>Asic1a<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice develop hypertension, whereas female\n                      <jats:italic>Asic1a<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice remain unaffected. This hypertension was associated with aldosterone excess, increased sympathetic activity, and evidence of aortic fibrosis, left ventricular hypertrophy and renal injury. Importantly, hyperaldosteronism occurred independently of the renin\u2013angiotensin system and was associated with blunting of angiotensin II\u2010induced hypertension. Prior to the onset of hypertension, 6\u2010month\u2010old male\n                      <jats:italic>Asic1a<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibit elevated corticosterone, hypokalaemia, reduced urine osmolality, increased pulse pressure and cardiomyocyte hypertrophy. Together, these findings identify ASIC1a as a novel, sex\u2010specific regulator of cardiovascular function, suggesting that ASIC1a deficiency may be a potential driver of endocrine\u2010related hypertension.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70231-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Extracellular acidosis, which occurs during pathological conditions such as ischaemia, inflammation and metabolic stress, contributes to the pathogenesis of cardiometabolic disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Acid\u2010sensing ion channels (ASICs) are key sensors of acidosis and important mediators of endothelium\u2010dependent vasodilatation; however, the role of ASIC1a in blood pressure regulation remains poorly understood.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Here we report that ASIC1a deficiency causes hypertension in aged male mice that is driven by an excess of aldosterone and increased sympathetic activity, while female mice remain unaffected. Hyperaldosteronism occurs independently of angiotensin II but is associated with elevated corticosterone that precedes the development of hypertension.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We further show that male, but not female, ASIC1a knockout mice have a reduced sensitivity to angiotensin II\u2010induced hypertension.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings identify ASIC1a as a novel, sex\u2010specific regulator of cardiovascular function, suggesting that ASIC1a deficiency contributes to endocrine\u2010related hypertension.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp289258","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T12:55:56Z","timestamp":1763211356000},"page":"172-192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Acid\u2010sensing ion channel 1a deficiency drives endocrine hypertension in male mice"],"prefix":"10.1113","volume":"604","author":[{"given":"Selina M.","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan N.","family":"Tuineau","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier A.","family":"DeLeon","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil D.","family":"Detweiler","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shristey","family":"Tamang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9028-4021","authenticated-orcid":false,"given":"Nancy L.","family":"Kanagy","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-4909","authenticated-orcid":false,"given":"Laura V.","family":"Gonzalez Bosc","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-6159","authenticated-orcid":false,"given":"Thomas C.","family":"Resta","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5725-4664","authenticated-orcid":false,"given":"Jay S.","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6269-2274","authenticated-orcid":false,"given":"Nikki L.","family":"Jernigan","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.20220"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.13922"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00637"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.17164"},{"issue":"1","key":"e_1_2_6_6_1","first-page":"A45","article-title":"Sex differences of Renal11\u03b2\u2010hsd1 and 11\u03b2\u2010hsd2 expression In A doca\u2010salt model of hypertension","volume":"78","author":"Belanger K.","year":"2021","journal-title":"Hypertension"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000134"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13533"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.05.023"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/179040"},{"key":"e_1_2_6_11_1","first-page":"661","article-title":"Primary aldosteronism","volume":"45","author":"Conn J. W.","year":"1955","journal-title":"Journal of Laboratory and Clinical Medicine"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12137"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192724"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13368"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2022"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2023.10.027"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315024"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202213173"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.989809"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09013"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2014.tb00569.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-015-8380-8"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.14521"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.027"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvac098"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.07.034"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.171330"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018226"},{"key":"e_1_2_6_29_1","first-page":"205","volume-title":"In histological and histochemical methods: Theory and practice","author":"Kiernan J. A.","year":"2008"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2009.08658.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14710"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032213"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-10-0607"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2005.03.044"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.007"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.05.002"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/1025389021000061165"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynpai.2025.100189"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1890"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00269.2013"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065370"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2014.03.002"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05221-2"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4009-13.2014"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-018-0192-8"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1557"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-77932-4_9"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.054360"},{"key":"e_1_2_6_49_1","first-page":"291","article-title":"Quantification of histochemical staining by color deconvolution","volume":"23","author":"Ruifrok A. C.","year":"2001","journal-title":"Analytical and Quantitative Cytology and Histology"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000330081"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01060"},{"key":"e_1_2_6_52_1","first-page":"887","article-title":"Genetics of primary aldosteronism","volume":"79","author":"Scholl U. I.","year":"2022","journal-title":"Hypertens Dallas Tex 1979"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07088"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2020.601939"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1665-11.2011"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2019-0351OC"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1276"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0573"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90995.2008"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.206946"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/1025389031000111302"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.592"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/386173a0"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2020.10.013"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00661-X"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1666"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4132-12.2013"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.08.026"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00193.2013"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308636100"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.025940"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2132"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP289258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T05:49:00Z","timestamp":1767937740000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP289258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,15]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1113\/JP289258"],"URL":"https:\/\/doi.org\/10.1113\/jp289258","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,15]]},"assertion":[{"value":"2025-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}