Mitigation and treatment of experimental radiation nephropathy have been shown using a multifraction total body irradiation (TBI) model with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II (AII) blockers. The ACE inhibitors have been used at a range of doses, and the AII blocker, L-158,809, is not approved for human use. Efficacy of these mitigating agents for use in radiation accident or terrorist event must be tested after single exposure and at doses approved for human use. Eighty-eight barrier-maintained WAG/Rij/MCW rats underwent single fraction TBI followed by syngeneic bone marrow transplant (BMT). TBI was 8, 9, 10, or 11 Gy. Captopril, 150 mg/L, or losartan, 100 mg/L, was added to the drinking water in half of the rats in each group. Rats were followed for renal function and survival. BUN data shown are at 17 weeks after TBI. At the 10 and 11 Gy doses, survival was significantly prolonged by captopril and losartan (p < .05). The 17-week BUN was less for the drug-treated rats at all radiation doses. We expect that complete 26-week follow-up will show significant function differences in all groups. We conclude that captopril and losartan are effective in mitigating experimental radiation nephropathy at doses compatible with human use.
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