{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:39:07Z","timestamp":1791308347442,"version":"4.3.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea government","award":["2014R1A2A1A11049900"],"award-info":[{"award-number":["2014R1A2A1A11049900"]}]},{"name":"Korea government","award":["2017R1A2B2002277"],"award-info":[{"award-number":["2017R1A2B2002277"]}]},{"name":"Korea government","award":["2016R1D1A1B03932771"],"award-info":[{"award-number":["2016R1D1A1B03932771"]}]},{"name":"Korea government","award":["2019R1I1A1A01057744"],"award-info":[{"award-number":["2019R1I1A1A01057744"]}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Abundant evidence indicates that oestrogen (E2) plays a protective role against hypertension. Yet, the mechanism underlying the antihypertensive effect of E2 is poorly understood. In this study, we sought to determine the mechanism through which E2 inhibits salt-dependent hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>To this end, we performed a series of in vivo and in vitro experiments employing a rat model of hypertension that is produced by deoxycorticosterone acetate (DOCA)-salt treatment after uninephrectomy. We found that E2 prevented DOCA-salt treatment from inducing hypertension, raising plasma arginine-vasopressin (AVP) level, enhancing the depressor effect of the V1a receptor antagonist (Phenylac1,D-Tyr(Et)2,Lys6,Arg8,des-Gly9)-vasopressin, and converting GABAergic inhibition to excitation in hypothalamic magnocellular AVP neurons. Moreover, we obtained results indicating that the E2 modulation of the activity and\/or expression of NKCC1 (Cl\u2212 importer) and KCC2 (Cl\u2212 extruder) underpins the effect of E2 on the transition of GABAergic transmission in AVP neurons. Lastly, we discovered that, in DOCA-salt-treated hypertensive ovariectomized rats, CLP290 (prodrug of the KCC2 activator CLP257, intraperitoneal injections) lowered blood pressure, and plasma AVP level and hyperpolarized GABA equilibrium potential to prevent GABAergic excitation from emerging in the AVP neurons of these animals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on these results, we conclude that E2 inhibits salt-dependent hypertension by suppressing GABAergic excitation to decrease the hormonal output of AVP neurons.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa271","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T07:10:15Z","timestamp":1599635415000},"page":"2263-2274","source":"Crossref","is-referenced-by-count":19,"title":["Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in magnocellular AVP neurons"],"prefix":"10.1093","volume":"117","author":[{"given":"Xiangyan","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine , 126-1 Anam-dong 5-ga, Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong Bin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine , 126-1 Anam-dong 5-ga, Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Na","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Section, Korea University Anam Hospital , Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Woo","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine , 126-1 Anam-dong 5-ga, Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Kyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine , 126-1 Anam-dong 5-ga, Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Hwa","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine , 126-1 Anam-dong 5-ga, Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine , 126-1 Anam-dong 5-ga, Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2467-3336","authenticated-orcid":false,"given":"Wan Joo","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Section, Korea University Anam Hospital , Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Chul","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine , 126-1 Anam-dong 5-ga, Seoul 136-705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1059-184X","authenticated-orcid":false,"given":"Christopher S","family":"Colwell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry 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