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In addition to these changes in renal hemodynamics, there were profound disturbances in renal signaling processes: phosphorylation of members of the MAPK and Akt signaling proteins occurred in the kidney in wild-type mice after ischemia, whereas such phosphorylation did not occur in the kidney in sickle mice after ischemia. ATP content in the postischemic kidney in sickle mice was less than half that observed in wild-type mice. Examination of the expression of candidate genes uncovered changes that may predispose to increased sensitivity of the kidney in sickle mice to ischemia: increased expression of inducible nitric oxide synthase and decreased expression of endothelial nitric oxide synthase, and increased expression of TNF-\u03b1. Inducibility of anti-inflammatory, cytoprotective genes, such as heme oxygenase-1 and IL-10, was not impaired in sickle mice after ischemia. We conclude that the kidney in SCD is remarkably vulnerable to acute ischemic insults. We speculate that such sensitivity of the kidney to ischemia in SCD may underlie the occurrence of acute kidney injury in patients with SCD and may set the stage for the emergence of chronic kidney disease in SCD.<\/jats:p>","DOI":"10.1152\/ajprenal.00631.2009","type":"journal-article","created":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T03:07:39Z","timestamp":1264648059000},"page":"F892-F899","source":"Crossref","is-referenced-by-count":25,"title":["Early and prominent alterations in hemodynamics, signaling, and gene expression following renal ischemia in sickle cell disease"],"prefix":"10.1152","volume":"298","author":[{"given":"Julio P.","family":"Juncos","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph P.","family":"Grande","sequence":"additional","affiliation":[{"name":"Department of Pathology, 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