{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T15:56:13Z","timestamp":1783785373623,"version":"3.55.0"},"reference-count":66,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,11,8]]},"abstract":"<jats:sec>\n            <jats:title>Rationale:<\/jats:title>\n            <jats:p>Obesity leads to resistant hypertension and mechanisms are poorly understood, but high plasma levels of leptin have been implicated. Leptin increases blood pressure acting both centrally in the dorsomedial hypothalamus and peripherally. Sites of the peripheral hypertensive effect of leptin have not been identified. We previously reported that leptin enhanced activity of the carotid sinus nerve, which transmits chemosensory input from the carotid bodies (CBs) to the medullary centers, and this effect was abolished by nonselective blockers of Trp (transient receptor potential) channels. We searched our mouse CB transcriptome database and found that the Trpm7 (transient receptor potential melastatin 7) channel was the most abundant Trp channel.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>To examine if leptin induces hypertension acting on the CB Trpm7.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              C57BL\/6J (n=79), leptin receptor (\n              <jats:italic>LepR<\/jats:italic>\n              <jats:sup>\n                <jats:italic>b<\/jats:italic>\n              <\/jats:sup>\n              ) deficient\n              <jats:italic>db\/db<\/jats:italic>\n              mice (n=22), and LepRb-EGFP (n=4) mice were used. CB\n              <jats:italic>Trpm7<\/jats:italic>\n              and\n              <jats:italic>LepR<\/jats:italic>\n              <jats:sup>\n                <jats:italic>b<\/jats:italic>\n              <\/jats:sup>\n              gene expression was determined and immunohistochemistry was performed; CB glomus cells were isolated and Trpm7-like current was recorded. Blood pressure was recorded continuously in (1) leptin-treated C57BL\/6J mice with intact and denervated CB; (2) leptin-treated C57BL\/6J mice, which also received a nonselective Trpm7 blocker FTY720 administered systemically or topically to the CB area; (3) leptin-treated C57BL\/6J mice transfected with\n              <jats:italic>Trpm7<\/jats:italic>\n              small hairpin RNA to the CB, and (4)\n              <jats:italic>Lepr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>b<\/jats:italic>\n              <\/jats:sup>\n              deficient obese\n              <jats:italic>db\/db<\/jats:italic>\n              mice before and after\n              <jats:italic>Lepr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>b<\/jats:italic>\n              <\/jats:sup>\n              expression in CB. Leptin receptor and Trpm7 colocalized in the CB glomus cells. Leptin induced a nonselective cation current in these cells, which was inhibited by Trpm7 blockers. Leptin induced hypertension in C57BL\/6J mice, which was abolished by CB denervation, Trpm 7 blockers, and\n              <jats:italic>Trpm7<\/jats:italic>\n              small hairpin RNA applied to CBs.\n              <jats:italic>Lepr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>b<\/jats:italic>\n              <\/jats:sup>\n              overexpression in CB of\n              <jats:italic>Lepr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>b<\/jats:italic>\n              <\/jats:sup>\n              -deficient\n              <jats:italic>db\/db<\/jats:italic>\n              mice demethylated the\n              <jats:italic>Trpm7<\/jats:italic>\n              promoter, increased\n              <jats:italic>Trpm7<\/jats:italic>\n              gene expression, and induced hypertension.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>We conclude that leptin induces hypertension acting on Trmp7 in CB, which opens horizons for new therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.119.315338","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T13:47:47Z","timestamp":1569246467000},"page":"989-1002","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body"],"prefix":"10.1161","volume":"125","author":[{"given":"Mi-Kyung","family":"Shin","sequence":"first","affiliation":[{"name":"From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (M.-K.S., C.G., B.H.Y.Y., L.J.K., J.S.K.S., V.Y.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candela Caballero","family":"Eraso","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dico-Quir\u00fargica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Hospital Universitario Virgen del Roc\u00edo\/Universidad de Sevilla, Spain (C.C.E.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ping","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China (Y.-P.M., X.-R.L., Z.-J.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjuan","family":"Gu","sequence":"additional","affiliation":[{"name":"From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (M.-K.S., C.G., B.H.Y.Y., L.J.K., J.S.K.S., V.Y.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie H.Y.","family":"Yeung","sequence":"additional","affiliation":[{"name":"From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (M.-K.S., C.G., B.H.Y.Y., L.J.K., J.S.K.S., V.Y.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenise J.","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (M.-K.S., C.G., B.H.Y.Y., L.J.K., J.S.K.S., V.Y.P.)"},{"name":"Departamento de Psicobiologia, Universidade Federal de S\u00e3o Paulo, Brazil (L.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ru","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China (Y.-P.M., X.-R.L., Z.-J.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Juan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China (Y.-P.M., X.-R.L., Z.-J.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omkar","family":"Paudel","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (O.P., L.E.P., M.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Pichard","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (O.P., L.E.P., M.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiko","family":"Shirahata","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (O.P., L.E.P., M.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Yee","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.K.","family":"Sham","sequence":"additional","affiliation":[{"name":"From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (M.-K.S., C.G., B.H.Y.Y., L.J.K., J.S.K.S., V.Y.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod Y.","family":"Polotsky","sequence":"additional","affiliation":[{"name":"From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (M.-K.S., C.G., B.H.Y.Y., L.J.K., J.S.K.S., V.Y.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.6228"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R110.113175"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904130"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0b013e328353ad6e"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2004.05.017"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.44"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624777"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2008.26788B"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340503"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1195-1155"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-589"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0196-9781(99)00139-4"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.2741\/3885"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2014.04.003"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000151325.83008.b4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2009.244"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.148213"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.058"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81294-5"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.02.028"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.11.018"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP276900"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2012.09.006"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00484.2014"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00444.2012"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22528"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00249"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18440-1_17"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP275362"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00383.2006"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01855.x"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12012"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701149104"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.57.1.75"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1159\/000088358"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsy089"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.237800"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2016.06.004"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1463"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.116.07232"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws342"},{"key":"e_1_3_4_43_2","first-page":"568","article-title":"[Polygraphic study of diurnal and nocturnal (hypnic and respiratory) episodal manifestations of Pickwick syndrome].","volume":"112","author":"Gastaut H","year":"1965","unstructured":"Gastaut, H, Tassinari, CA, Duron, B. [Polygraphic study of diurnal and nocturnal (hypnic and respiratory) episodal manifestations of Pickwick syndrome]. Rev Neurol (Paris). 1965;112:568\u2013579.","journal-title":"Rev Neurol (Paris)"},{"key":"e_1_3_4_44_2","volume-title":"In: Comprehensive Physiology","author":"Prabhakar NR","year":"2011","unstructured":"Prabhakar, NR, Peng, Y-J, Kumar, GK, Nanduri, J. Peripheral chemoreception and arterial pressure responses to intermittent hypoxia. In: Comprehensive Physiology. John Wiley & Sons Inc.; 2011."},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.72.5.1978"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.114033"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4173"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.98.8.772"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3395"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2014.07.001"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.151068"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(03)01017-1"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2395"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1488-0"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb781"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2016.1164373"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.7.4660"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.670877"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605300200"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2008.04.005"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2008.232"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.2144\/000113999"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-016-0239-9"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes9080410"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00779.2005"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909494"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01314-8"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.119.315338","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:25:55Z","timestamp":1715574355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.119.315338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,8]]},"references-count":66,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11,8]]}},"alternative-id":["10.1161\/CIRCRESAHA.119.315338"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.119.315338","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,8]]},"assertion":[{"value":"2019-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}