{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:40:44Z","timestamp":1792597244914,"version":"4.5.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":1461,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","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":["kidney-international.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Kidney International"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1016\/j.kint.2021.03.025","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T01:53:52Z","timestamp":1617674032000},"page":"311-320","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":43,"title":["A small molecule inhibitor of the chloride channel TMEM16A blocks vascular smooth muscle contraction and lowers blood pressure in spontaneously hypertensive rats"],"prefix":"10.1016","volume":"100","author":[{"given":"Onur","family":"Cil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry R.","family":"Askew Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel N.","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pyone","family":"Myat Thwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc O.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Haggie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain A.","family":"Greenwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth P.","family":"Roos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Verkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.kint.2021.03.025_bib1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1001\/jama.2013.284427","article-title":"2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)","volume":"311","author":"James","year":"2014","journal-title":"JAMA"},{"key":"10.1016\/j.kint.2021.03.025_bib2","first-page":"703","article-title":"Vital signs: awareness and treatment of uncontrolled hypertension among adults - United States, 2003\u20132010","volume":"61","year":"2012","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"10.1016\/j.kint.2021.03.025_bib3","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1056\/NEJMoa1511939","article-title":"A\u00a0randomized trial of intensive versus standard blood-pressure control","volume":"373","year":"2015","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.kint.2021.03.025_bib4","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1161\/HYPERTENSIONAHA.111.170308","article-title":"Prevalence of resistant hypertension in the United States, 2003-2008","volume":"57","author":"Persell","year":"2011","journal-title":"Hypertension"},{"key":"10.1016\/j.kint.2021.03.025_bib5","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.mayocp.2013.06.017","article-title":"Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system","volume":"88","author":"Sim","year":"2013","journal-title":"Mayo Clin Proc"},{"key":"10.1016\/j.kint.2021.03.025_bib6","doi-asserted-by":"crossref","first-page":"C948","DOI":"10.1152\/ajpcell.00018.2010","article-title":"Expression profile and protein translation of TMEM16A in murine smooth muscle","volume":"299","author":"Davis","year":"2010","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.kint.2021.03.025_bib7","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1111\/j.1476-5381.2012.02199.x","article-title":"Potent vasorelaxant activity of the TMEM16A inhibitor T16A(inh) -A01","volume":"168","author":"Davis","year":"2013","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.kint.2021.03.025_bib8","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1113\/jphysiol.2010.189506","article-title":"TMEM16A\/anoctamin 1 protein mediates calcium-activated chloride currents in pulmonary arterial smooth muscle cells","volume":"588","author":"Manoury","year":"2010","journal-title":"J\u00a0Physiol"},{"key":"10.1016\/j.kint.2021.03.025_bib9","doi-asserted-by":"crossref","first-page":"H1819","DOI":"10.1152\/ajpheart.00404.2011","article-title":"TMEM16A channels generate Ca2\u207a-activated Cl\u207b currents in cerebral artery smooth muscle cells","volume":"301","author":"Thomas-Gatewood","year":"2011","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.kint.2021.03.025_bib10","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/jcp.25823","article-title":"Molecular, biophysical, and pharmacological properties of calcium-activated chloride channels","volume":"233","author":"Kamaleddin","year":"2018","journal-title":"J\u00a0Cell Physiol"},{"key":"10.1016\/j.kint.2021.03.025_bib11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0079-6107(00)00024-9","article-title":"Chloride in smooth muscle","volume":"74","author":"Chipperfield","year":"2000","journal-title":"Prog Biophys Mol Biol"},{"key":"10.1016\/j.kint.2021.03.025_bib12","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1139\/y05-040","article-title":"Regulation of calcium-activated chloride channels in smooth muscle cells: a complex picture is emerging","volume":"83","author":"Leblanc","year":"2005","journal-title":"Can J Physiol Pharmacol"},{"key":"10.1016\/j.kint.2021.03.025_bib13","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1172\/JCI70025","article-title":"Disruption of vascular Ca2+-activated chloride currents lowers blood pressure","volume":"124","author":"Heinze","year":"2014","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.kint.2021.03.025_bib14","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1074\/jbc.M110.175109","article-title":"TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells","volume":"286","author":"Namkung","year":"2011","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.kint.2021.03.025_bib15","doi-asserted-by":"crossref","first-page":"4626","DOI":"10.1021\/acs.jmedchem.7b00020","article-title":"Substituted 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides as inhibitors of the calcium-activated chloride channel transmembrane protein 16A (TMEM16A)","volume":"60","author":"Truong","year":"2017","journal-title":"J\u00a0Med Chem"},{"key":"10.1016\/j.kint.2021.03.025_bib16","doi-asserted-by":"crossref","first-page":"11247","DOI":"10.1096\/fj.201900858R","article-title":"Slowed gastric emptying and improved oral glucose tolerance produced by a nanomolar-potency inhibitor of calcium-activated chloride channel TMEM16A","volume":"33","author":"Cil","year":"2019","journal-title":"FASEB J"},{"key":"10.1016\/j.kint.2021.03.025_bib17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ymgme.2005.05.003","article-title":"Cardiac manifestations in the mouse model of mucopolysaccharidosis I","volume":"86","author":"Jordan","year":"2005","journal-title":"Mol Genet Metab"},{"key":"10.1016\/j.kint.2021.03.025_bib18","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/ajh.2008.301","article-title":"Validation of volume\u2013pressure recording tail-cuff blood pressure measurements","volume":"21","author":"Feng","year":"2008","journal-title":"Am J Hypertens"},{"key":"10.1016\/j.kint.2021.03.025_bib19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/9780470942390.mo100149","article-title":"Arterial pressure monitoring in mice","volume":"1","author":"Zhao","year":"2011","journal-title":"Curr Protoc Mouse Biol"},{"key":"10.1016\/j.kint.2021.03.025_bib20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.kint.2018.12.033","article-title":"Men, mice, and blood pressure: telemetry?","volume":"96","author":"Luft","year":"2019","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2021.03.025_bib21","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1111\/bph.14598","article-title":"TMEM16A is implicated in the regulation of coronary flow and is altered in hypertension","volume":"176","author":"Askew Page","year":"2019","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.kint.2021.03.025_bib22","first-page":"1","article-title":"Do resistance vessel abnormalities contribute to the elevated blood pressure of spontaneously-hypertensive rats? a review of some of the evidence","volume":"20","author":"Mulvany","year":"1983","journal-title":"Blood Vessels"},{"key":"10.1016\/j.kint.2021.03.025_bib23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/bcpt.12984","article-title":"Variable contribution of TMEM16A to tone in murine arterial vasculature","volume":"123","author":"Jensen","year":"2018","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1016\/j.kint.2021.03.025_bib24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.yjmcc.2015.02.020","article-title":"Overexpression of ANO1\/TMEM16A, an arterial Ca+2-activated Cl- channel, contributes to spontaneous hypertension","volume":"82","author":"Wang","year":"2015","journal-title":"J\u00a0Mol Cell Cardiol"},{"key":"10.1016\/j.kint.2021.03.025_bib25","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1111\/j.1476-5381.1996.tb15507.x","article-title":"Effect of niflumic acid on noradrenaline-induced contractions of the rat aorta","volume":"118","author":"Criddle","year":"1996","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.kint.2021.03.025_bib26","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/j.2040-4603.2017.tb00747.x","article-title":"Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles","volume":"7","author":"Tykocki","year":"2017","journal-title":"Compr Physiol"},{"key":"10.1016\/j.kint.2021.03.025_bib27","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s00424-013-1382-1","article-title":"TMEM16A knockdown abrogates two different Ca(2+)-activated Cl (-) currents and contractility of smooth muscle in rat mesenteric small arteries","volume":"466","author":"Dam","year":"2014","journal-title":"Pflugers Arch"},{"key":"10.1016\/j.kint.2021.03.025_bib28","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.3892\/mmr.2016.4979","article-title":"TMEM16A contributes to angiotensin II-induced cerebral vasoconstriction via the RhoA\/ROCK signaling pathway","volume":"13","author":"Li","year":"2016","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.kint.2021.03.025_bib29","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1161\/HYPERTENSIONAHA.118.09909","article-title":"Hemodynamic response to gabapentin in conscious spontaneously hypertensive rats","volume":"72","author":"Behuliak","year":"2018","journal-title":"Hypertension"},{"key":"10.1016\/j.kint.2021.03.025_bib30","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/jcp.24709","article-title":"Characterization of cardiac anoctamin1 Ca2\u207a-activated chloride channels and functional role in ischemia-induced arrhythmias","volume":"230","author":"Ye","year":"2015","journal-title":"J\u00a0Cell Physiol"},{"key":"10.1016\/j.kint.2021.03.025_bib31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.yjmcc.2016.05.006","article-title":"Sarcolemmal Ca(2+)-entry through L-type Ca(2+) channels controls the profile of Ca(2+)-activated Cl(-) current in canine ventricular myocytes","volume":"97","author":"Horv\u00e1th","year":"2016","journal-title":"J\u00a0Mol Cell Cardiol"},{"key":"10.1016\/j.kint.2021.03.025_bib32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.yjmcc.2017.06.014","article-title":"Ca(2+)-activated Cl(-) current is antiarrhythmic by reducing both spatial and temporal heterogeneity of cardiac repolarization","volume":"109","author":"Hegyi","year":"2017","journal-title":"J\u00a0Mol Cell Cardiol"},{"key":"10.1016\/j.kint.2021.03.025_bib33","doi-asserted-by":"crossref","first-page":"1800965","DOI":"10.1183\/13993003.00965-2018","article-title":"Targeting TMEM16A to reverse vasoconstriction and remodelling in idiopathic pulmonary arterial hypertension","volume":"53","author":"Papp","year":"2019","journal-title":"Eur Respir J"},{"key":"10.1016\/j.kint.2021.03.025_bib34","doi-asserted-by":"crossref","first-page":"16354","DOI":"10.1073\/pnas.1214596109","article-title":"Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction","volume":"109","author":"Huang","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.kint.2021.03.025_bib35","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1073\/pnas.1415739112","article-title":"A\u00a0fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland","volume":"112","author":"Catal\u00e1n","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.kint.2021.03.025_bib36","doi-asserted-by":"crossref","first-page":"C767","DOI":"10.1152\/ajpcell.00195.2012","article-title":"Regional differences in rat conjunctival ion transport activities","volume":"303","author":"Yu","year":"2012","journal-title":"Am J Physiol Cell Physiol"}],"container-title":["Kidney International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0085253821003604?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0085253821003604?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:59:01Z","timestamp":1758761941000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0085253821003604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["S0085253821003604"],"URL":"https:\/\/doi.org\/10.1016\/j.kint.2021.03.025","relation":{},"ISSN":["0085-2538"],"issn-type":[{"value":"0085-2538","type":"print"}],"subject":[],"published":{"date-parts":[[2021,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A small molecule inhibitor of the chloride channel TMEM16A blocks vascular smooth muscle contraction and lowers blood pressure in spontaneously hypertensive rats","name":"articletitle","label":"Article Title"},{"value":"Kidney International","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.kint.2021.03.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 International Society of Nephrology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}