{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:02:54Z","timestamp":1792029774975,"version":"4.4.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury. MR blockade by the novel nonsteroidal MR antagonist, finerenone, or genetic deletion of MR in SMCs associated with weaker oxidative stress production. Moreover, ischemic kidneys had higher levels of Rac1-GTP, required for NADPH oxidase activation, than sham control kidneys, and genetic deletion of Rac1 in SMCs protected against AKI. Furthermore, genetic deletion of MR in SMCs blunted the production of Rac1-GTP after IR. Pharmacologic inhibition of MR also prevented AKI induced by IR in the Large White pig. Altogether, we show that MR antagonism, or deletion of the MR gene in SMCs, limited the renal injury induced by IR through effects on Rac1-mediated MR signaling. The benefits of MR antagonism in the pig provide a rational basis for future clinical trials assessing the benefits of this approach in patients with IR-mediated AKI.<\/jats:p>","DOI":"10.1681\/asn.2016040477","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T22:10:19Z","timestamp":1484345419000},"page":"1216-1226","source":"Crossref","is-referenced-by-count":86,"title":["Benefit of Mineralocorticoid Receptor Antagonism in AKI: Role of Vascular Smooth Muscle Rac1"],"prefix":"10.1681","volume":"28","author":[{"given":"Jonatan","family":"Barrera-Chimal","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Scientifique 1138, Team 1, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwennan","family":"Andr\u00e9-Gr\u00e9goire","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Scientifique 1138, Team 1, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Nguyen dinh Cat","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Scientifique 1138, Team 1, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian M.","family":"Lechner","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Scientifique 1138, Team 1, 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