{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:11Z","timestamp":1792042271451,"version":"4.4.0"},"reference-count":60,"publisher":"American Physiological Society","issue":"10","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["R01DK102429-01"],"award-info":[{"award-number":["R01DK102429-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["2R01DK067299-06A2"],"award-info":[{"award-number":["2R01DK067299-06A2"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>The renal mechanisms responsible for angiotensin II (ANG II)-induced hypertension remain incompletely understood. The present study tested the hypothesis that the Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchanger 3 (NHE3) is required for ANG II-induced hypertension in mice. Five groups of wild-type ( Nhe3<jats:sup>+\/+<\/jats:sup>) and Nhe3<jats:sup>\u2212\/\u2212<\/jats:sup>mice were treated with vehicle or high pressor doses of ANG II (1.5 mg\/kg\/day ip, via minipump for 2 wk, or 10 pmol\/min iv for 30 min). Under basal conditions, Nhe3<jats:sup>\u2212\/\u2212<\/jats:sup>mice had significantly lower systolic blood pressure (SBP) and mean intra-arterial pressure (MAP) ( P &lt; 0.01), 24 h urine ( P &lt; 0.05), urinary Na<jats:sup>+<\/jats:sup>( P &lt; 0.01) and urinary K<jats:sup>+<\/jats:sup>excretion ( P &lt; 0.01). In response to ANG II, SBP and MAP markedly increased in Nhe3<jats:sup>+\/+<\/jats:sup>mice in a time-dependent manner, as expected ( P &lt; 0.01). However, these acute and chronic pressor responses to ANG II were significantly attenuated in Nhe3<jats:sup>\u2212\/\u2212<\/jats:sup>mice ( P &lt; 0.01). Losartan blocked ANG II-induced hypertension in Nhe3<jats:sup>+\/+<\/jats:sup>mice but induced marked mortality in Nhe3<jats:sup>\u2212\/\u2212<\/jats:sup>mice. The attenuated pressor responses to ANG II in Nhe3<jats:sup>\u2212\/\u2212<\/jats:sup>mice were associated with marked compensatory humoral and renal responses to genetic loss of intestinal and renal NHE3. These include elevated basal plasma ANG II and aldosterone and kidney ANG II levels, salt wasting from the intestines, increased renal AQP1, Na<jats:sup>+<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, and Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase expression, and increased PKC\u03b1, mitogen-activated protein kinases ERK1\/2, and glycogen synthase kinase 3\u03b1\u03b2 signaling proteins in the proximal tubules ( P &lt; 0.01). We concluded that NHE3 in proximal tubules of the kidney, along with NHE3 in intestines, is required for maintaining basal blood pressure as well as the full development of ANG II-induced hypertension.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00056.2015","type":"journal-article","created":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T01:59:36Z","timestamp":1438739976000},"page":"479-487","source":"Crossref","is-referenced-by-count":33,"title":["Role of the Na<sup>+<\/sup>\/H<sup>+<\/sup>exchanger 3 in angiotensin II-induced hypertension"],"prefix":"10.1152","volume":"47","author":[{"given":"Xiao C.","family":"Li","sequence":"first","affiliation":[{"name":"Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology; Division of Nephrology, Department of Medicine; University of Mississippi Medical Center, Jackson, Mississippi; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Shull","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Miguel-Qin","sequence":"additional","affiliation":[{"name":"Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology; Division of Nephrology, Department of Medicine; University of Mississippi Medical Center, Jackson, Mississippi; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia L.","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology; Division of Nephrology, Department of Medicine; University of Mississippi Medical Center, Jackson, Mississippi; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112602"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1159\/000049895"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.404"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1983.245.6.F647"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00121.2011"},{"key":"B6","first-page":"86","volume":"11","author":"Berry CA","year":"1991","journal-title":"Semin Nephrol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.273.2.F289"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1992.263.1.F135"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1989.208"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.189141"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00189.x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-009-0086-6"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0907219"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00240.2006"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.20.7917"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.2063193"},{"key":"B17","volume-title":"Hypertension: Pathophysiology, Diagnosis, and Management","author":"Guyton AC","year":"1995"},{"key":"B18","first-page":"43","volume":"15","author":"Hayashi M","year":"1997","journal-title":"J Hypertens"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.133066"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.464"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.834"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00406.x"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.4.F718"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00178.2002"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ng.384"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90734.2008"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00219.2012"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.134"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.161"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00338.2012"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.201590"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192667"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.3.F447"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3281fc975a"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00002.2010"},{"key":"B36","volume-title":"Brenner and Rector's The Kidney","author":"Mount DB","year":"2007","edition":"8"},{"key":"B37","volume-title":"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure","author":"National Heart, Lung, and Blood Institute","year":"2003"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/ng.361"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00209.2004"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00075.2010"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012088488-9.50055-3"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00515.2014"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1983.244.5.F461"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.269.3.F374"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00464.2009"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2012.260"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1984.78"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/969"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.278.3.F375"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00345.2006"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.2.F298"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e32832f5775"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012088488-9.50033-4"},{"key":"B54","volume-title":"The Kidney: Physiology and Pathophysiology","author":"Wilcox CS","year":"1992"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00418.2002"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00298.2001"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000125428.28861.11"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.04887"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1161\/hy0102.100780"},{"key":"B60","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/cphy.c110061","volume":"3","author":"Zhuo JL","year":"2013","journal-title":"Compr Physiol"}],"container-title":["Physiological Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/physiolgenomics.00056.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T23:50:04Z","timestamp":1653004204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/physiolgenomics.00056.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10]]},"references-count":60,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1152\/physiolgenomics.00056.2015"],"URL":"https:\/\/doi.org\/10.1152\/physiolgenomics.00056.2015","relation":{},"ISSN":["1094-8341","1531-2267"],"issn-type":[{"value":"1094-8341","type":"print"},{"value":"1531-2267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10]]}}}