{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:27:37Z","timestamp":1785558457539,"version":"3.56.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,23]],"date-time":"2012-04-23T00:00:00Z","timestamp":1335139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:list>\n<jats:list-item><jats:p>Vascular endothelial growth factor inhibitors (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>i) are known to cause hypertension and renal injury that severely limits their use as an anticancer therapy. We hypothesized that the angiotensin\u2010converting enzyme inhibitor captopril not only prevents hypertension, but also decreases renal injury caused by the <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>i sorafenib.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rats were administered sorafenib (20\u00a0mg\/kg per day) alone or in combination with captopril (40\u00a0mg\/kg per day) for 4\u00a0weeks. Sorafenib administration increased blood pressure, which plateaued by day 10.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Concurrent treatment with captopril for 4\u00a0weeks resulted in a 30\u00a0mmHg decrease in blood pressure compared with sorafenib alone (155\u00a0\u00b1\u00a05 vs 182\u00a0\u00b1\u00a06\u00a0mmHg, respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Furthermore, concurrent captopril treatment reduced albuminuria by 50% compared with sorafenib alone (20\u00a0\u00b1\u00a08 vs 42\u00a0\u00b1\u00a09\u00a0mg\/day, respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and reduced nephrinuria by eightfold (280\u00a0\u00b1\u00a096 vs 2305\u00a0\u00b1\u00a0665\u00a0\u03bcg\/day, respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Glomerular injury, thrombotic microangiopathy and tubular cast formation were also decreased in captopril\u2010treated rats administered sorafenib. Renal autoregulatory efficiency was determined by evaluating the afferent arteriolar constrictor response to <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>. Sorafenib administration attenuated the vasoconstriction to <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>, whereas concurrent captopril treatment improved <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> reactivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, captopril attenuated hypertension and renal injury and improved renal autoregulatory capacity in rats administered sorafenib. These findings indicate that captopril treatment, in addition to alleviating the detrimental side\u2010effect of hypertension, decreases the renal injury associated with anticancer <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>i therapies such as sorafenib.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1111\/j.1440-1681.2012.05699.x","type":"journal-article","created":{"date-parts":[[2012,3,23]],"date-time":"2012-03-23T12:03:53Z","timestamp":1332504233000},"page":"454-461","source":"Crossref","is-referenced-by-count":26,"title":["Captopril attenuates hypertension and renal injury induced by the vascular endothelial growth factor inhibitor sorafenib"],"prefix":"10.1111","volume":"39","author":[{"given":"Tasuku","family":"Nagasawa","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Medical College of Wisconsin Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Abdul","family":"Hye 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