Brief pharmacological intervention in experimental radiation nephropathy.
Brief postirradiation treatment with an angiotensin-converting enzyme (ACE) inhibitor has been shown to be effective in reducing the severity of radiation nephropathy in rats. The efficacy of brief treatment with an ACE inhibitor was shown to be greatest when the animals were young when irradiated and when the treatment was given 4 to 10 weeks after bone marrow transplantation (BMT). In further studies with a BMT nephropathy model, we have shown that brief treatment with an angiotensin II type I receptor antagonist (AII blocker) is even more effective than brief treatment with an ACE inhibitor. We have also shown that an NO synthase inhibitor, which exacerbated radiation nephropathy when given continuously, has no effect when given during the postirradiation interval when ACE inhibitors and AII blockers were most effective. Studies also showed that the loss of efficacy of brief treatment with increased age at irradiation parallels the decrease in radiosensitivity that occurs with increasing age at irradiation, but that this decrease in radiosensitivity is not sufficient to explain the loss of efficacy of brief treatment. These data indicate that the renin-angiotensin system is important in the expression of renal radiation injury, particularly between 4 and 10 weeks after irradiation.
Moulder
J E
JE
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA.
Fish
B L
BL
Cohen
E P
EP
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000009:adverse effects; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats; D014916:Whole-Body Irradiation
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester