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-converting enzyme can prevent the structural and functional changes that occur after renal irradiation, which suggests that the renin-angiotensin system plays a key role in their evolution. We therefore evaluated captopril, used for short intervals, in a total body irradiation model of radiation nephropathy. Irradiated 7- to 8-week-old rats that were treated with captopril from 3.5 to 9.5 weeks after irradiation had better kidney function and survival than irradiated animals treated at earlier or later intervals. At 26 weeks after irradiation, kidney function of these animals was similar to that of irradiated animals treated continuously with captopril, but their subsequent survival was less. Animals 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 animals treated at earlier or later intervals. Irradiated 15-week-old animals had significant functional and survival benefit from continuous captopril treatment but no protection from a 6-week interval of therapy. We conclude that radiation nephropathy may be significantly attenuated 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-angiotensin system is important in the sequential expression of renal radiation injury, particularly between 3.5 and 9.5 weeks after irradiation.
Cohen
E P
EP
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
Fish
B L
BL
Moulder
J E
JE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016026:Bone Marrow Transplantation; D002216:Captopril / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D007677:Kidney Function Tests; D009393:Nephritis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate; D014916:Whole-Body Irradiation
D000806:Angiotensin-Converting Enzyme Inhibitors; D011837:Radiation-Protective Agents; D002216:Captopril