{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T02:51:46Z","timestamp":1761706306733},"reference-count":26,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p> The aims of this study were to 1) determine whether renal localization of aliskiren and its antihypertensive and renoprotective effects persist after administration of the drug is stopped and 2) define the renal localization of aliskiren by light microscopy autoradiography. Hypertensive double transgenic rats (dTGR) overexpressing genes for human renin and angiotensinogen were treated with aliskiren (3 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> sc; osmotic minipumps) or enalapril (18 mg\/l in drinking water). After a 2-wk treatment, dTGR were assigned to either continued treatment with aliskiren (\u201ccontinued\u201d), or to cessation of their respective treatment (\u201cstopped\u201d) for a 3-wk washout. One week of treatment with aliskiren and enalapril reduced blood pressure and albuminuria vs. baseline. After cessation of either treatment, blood pressure had returned to pretreatment levels and albuminuria remained relatively low for 1 wk, but rose thereafter similarly in both groups. In contrast, renal mRNA for transforming growth factor-\u03b2 and renal collagen IV was reduced by aliskiren (continued and stopped groups), but not after cessation of enalapril. Similar patterns were found for collagen IV protein expression. Even 3 wk after stopping aliskiren treatment, renal levels of the drug exceeded its IC<jats:sub>50<\/jats:sub>, whereas enalaprilat was not detected. To localize aliskiren accumulation, Wistar rats were treated with [<jats:sup>3<\/jats:sup>H]-aliskiren for 7 days. Autoradiography demonstrated specific labeling in glomeruli, arterioles, and afferent arterioles as well as in the distal nephron. Labeling could still be observed even after 7 days' washout. These results suggest that the renophilic properties of aliskiren are different from enalapril and could have contributed to the renoprotective mechanism of this renin inhibitor. <\/jats:p>","DOI":"10.1152\/ajprenal.00655.2012","type":"journal-article","created":{"date-parts":[[2013,8,8]],"date-time":"2013-08-08T02:22:30Z","timestamp":1375928550000},"page":"F1593-F1602","source":"Crossref","is-referenced-by-count":7,"title":["The direct renin inhibitor aliskiren localizes and persists in rat kidneys"],"prefix":"10.1152","volume":"305","author":[{"given":"David L.","family":"Feldman","sequence":"first","affiliation":[{"name":"Novartis Institutes for Biomedical Research, East Hanover, New Jersey;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Jin","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, East Hanover, New Jersey;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Xuan","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, East Hanover, New Jersey;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Persohn","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, East Hanover, New Jersey;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, East Hanover, New Jersey;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Schuetz","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, East Hanover, New Jersey;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joon-Keun","family":"Park","sequence":"additional","affiliation":[{"name":"Clinic for Nephrology and Hypertension, Hannover Medical School, Hannover, Germany; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik N.","family":"Muller","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Charit\u00e9 Medical Faculty and the Max-Delbr\u00fcck Center for Molecular Medicine, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich C.","family":"Luft","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Charit\u00e9 Medical Faculty and the Max-Delbr\u00fcck Center for Molecular Medicine, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2002000100003"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.164210"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.29.1.428"},{"key":"B4","first-page":"S224","volume":"11","author":"Danser AH","year":"1993","journal-title":"J Hypertens"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00362.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00266.2007"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.108845"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1988.254.6.F900"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.107268"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.123042"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32835e226b"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.2.587"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/344541a0"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.11.032"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.68"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000322242"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000179573.91016.3f"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000135678.20725.54"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00259.2010"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3109\/00498259609046705"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.04.038"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00391.2007"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.329"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.013797"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01451-7"},{"key":"B26","unstructured":"Young BHJ. 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