Ep. Cohen et al., SUCCESSFUL BRIEF CAPTOPRIL TREATMENT IN EXPERIMENTAL RADIATION NEPHROPATHY, The Journal of laboratory and clinical medicine, 129(5), 1997, pp. 536-547
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.