{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:45:03Z","timestamp":1785548703568,"version":"3.56.0"},"reference-count":75,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:p> Studies of Dahl salt-sensitive (SS) rats have shown that renal CD3<jats:sup>+<\/jats:sup> T cells and ED-1<jats:sup>+<\/jats:sup> macrophages are involved in the development of salt-sensitive hypertension and renal damage. The present study demonstrated that the increase in renal immune cells, which accompanies renal hypertrophy and albuminuria in high-salt diet-fed Dahl SS rats, is absent in Sprague-Dawley and SSBN13 rats that are protected from the SS disease phenotype. Flow cytometric analysis demonstrated that &gt;70% of the immune cells in the SS kidney are M1 macrophages. PCR profiling of renal myeloid cells showed a salt-induced upregulation in 9 of 84 genes related to Toll-like receptor signaling, with notable upregulation of the Toll-like receptor 4\/CD14\/MD2 complex. Because of the prominent increase in macrophages in the SS kidney, we used liposome-encapsulated clodronate (Clod) to deplete macrophages and assess their contribution to salt-sensitive hypertension and renal damage. Dahl SS animals were administered either Clod-containing liposomes (Clod-Lipo), Clod, or PBS-containing liposomes as a vehicle control. Clod-Lipo treatment depleted circulating and splenic macrophages by \u223c50%; however, contrary to our hypothesis, Clod-Lipo-treated animals developed an exacerbated salt-sensitive response with respect to blood pressure and albuminuria, which was accompanied by increased renal T and B cells. Interestingly, those treated with Clod also demonstrated an exacerbated phenotype, but it was less severe than Clod-Lipo-treated animals and independent of changes to the number of renal immune cells. Here, we have shown that renal macrophages in Dahl SS animals sustain a M1 proinflammatory phenotype in response to increased dietary salt and highlighted potential adverse effects of Clod-Lipo macrophage depletion. <\/jats:p>","DOI":"10.1152\/ajprenal.00096.2019","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T10:49:57Z","timestamp":1560941397000},"page":"F361-F374","source":"Crossref","is-referenced-by-count":50,"title":["Salt-sensitive increase in macrophages in the kidneys of Dahl SS rats"],"prefix":"10.1152","volume":"317","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3382-464X","authenticated-orcid":false,"given":"Daniel J.","family":"Fehrenbach","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Wauwatosa, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine M.","family":"Abais-Battad","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Wauwatosa, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Henry","family":"Dasinger","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Wauwatosa, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Wauwatosa, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Mattson","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Wauwatosa, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11994"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00201.2017"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.23.2.195"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1139\/Y10-051"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.01.010"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00061.2014"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3109\/10611869408996810"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.23.4.531"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-013-1144-z"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03530440061038"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.456"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01194"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00298.2009"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00600.x"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11485"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.4.378"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.0590041382.x"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nri978"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.15.6.803"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfw096"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.08.015"},{"key":"B22","first-page":"130","volume":"125","author":"Harrison DG","year":"2014","journal-title":"Trans Am Clin Climatol Assoc"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2017.10.011"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-019-0907-1"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000142893.08655.96"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.1.484"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0b013e328356062e"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00473"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.03.023"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03663"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000154784.14018.5f"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.5604\/17322693.1150133"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6549242"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(78)90045-1"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17741-1"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1212606"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1159\/000495276"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61766-8"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.02.076"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.00181"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13593"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2008.01.006"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.143339"},{"key":"B44","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.compbiomed.2015.04.033","volume":"65","author":"Makidon PE","year":"2015","journal-title":"Comp Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145946"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.12703\/P6-13"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00258.2014"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90341.2008"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000228320.23697.29"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00151.2003"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00304.2012"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.13.2.122"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.2131\/jts.43.299"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)05189-1"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-8-76"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00449.2017"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00821.2007"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.356"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00792.2018"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03581"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61468-9"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300421"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpu142"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2013.248"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3791\/54599"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02191"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00049.2010"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-011-0553-7"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2013.02.003"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00429.2007"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0110-2"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00283.2015"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00484.2014"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.429"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00096.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:25:10Z","timestamp":1567959910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00096.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,1]]},"references-count":75,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,8,1]]}},"alternative-id":["10.1152\/ajprenal.00096.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00096.2019","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,1]]}}}