SUCCESSFUL BRIEF CAPTOPRIL TREATMENT IN EXPERIMENTAL RADIATION NEPHROPATHY

Experimental renal irradiation is followed by a well-defined sequence of events leading to kidney failure. Inhibitors of angiotensin-convert ing enzyme can prevent the structural and functional changes that occu r after renal irradiation, which suggests that the renin-angiotensin s ystem plays a key role in their evolution. We therefore evaluated capt opril, used for short intervals, in a total body irradiation model of radiation nephropathy. Irradiated 7- to 8-week-old rats that were trea ted with captopril from 3.5 to 9.5 weeks after irradiation had better kidney function and survival than irradiated animals treated at earlie r or later intervals. At 26 weeks after irradiation, kidney function o f these animals was similar to that of irradiated animals treated cont inuously with captopril, but their subsequent survival was less. Anima ls irradiated at 7 to 8 weeks of age and treated with captopril from 6 to 9 weeks after irradiation had better function and survival than an imals treated at earlier or later intervals. Irradiated 15-week-old an imals had significant functional and survival benefit from continuous captopril treatment but no protection from a 6-week interval of therap y. We conclude that radiation nephropathy may be significantly attenua ted by the use of captopril from 3.5 to 9.5 weeks after irradiation in young animals. Although older animals did not appear to benefit from a short course of captopril, these data suggest that the renin-angiote nsin system is important in the sequential expression of renal radiati on injury, particularly between 3.5 and 9.5 weeks after irradiation.