Captopril preserves function and ultrastructure in experimental radiation nephropathy.
Captopril protects rat lung from radiation-induced pneumonitis and fibrosis and preserves function and survival in experimental radiation nephropathy. This study determined the structural benefit of captopril used preventively in radiation nephropathy. Twenty-eight Wag/RijMCW rats, divided in six groups, received 0 to 17 Gray total body irradiation followed by syngeneic bone marrow transplant. Captopril 0, 62.5, 125, 250, or 500 mg/l was given in the drinking water from the time of irradiation, and the rats were killed at 20 weeks. Using light and electron microscopy, kidneys of irradiated no-drug rats showed glomerular tuft capsular adhesions and hyalinization, focal tubular necrosis, severe interstitial fibrosis, and marked thickening and hyaline degeneration of the wall of interlobular arteries and arterioles, with intimal proliferation and periadventitial edema and inflammation. Lumens of the smaller arteries were often occluded. Significant collagen deposition was present in glomeruli, interstitium, and adventitia of interlobular arteries. Marked reduction of glomerular, tubular, vascular, and interstitial damage was seen in irradiated, captopril-treated animals, with only mild focal tubular interstitial injury and fibrosis seen. alpha smooth muscle actin-positive cells, probably myofibroblasts, were enhanced in the irradiated kidneys, and this expression was reduced in a dose-related fashion by captopril. There was also reduction in the arteriolar wall thickening, luminal occlusion, and collagen deposition in captopril-treated animals. The presence of elastin was not affected by radiation or drug treatment. Blood pressure and azotemia were lower and survival was higher in irradiated drug-treated rats compared with irradiated no-drug rats. We conclude that captopril exerts significant functional and structural protection against renal radiation injury. There was notable reduction in radiation-induced fibrosis in captopril-treated animals in this model, as in experimental lung radiation injury.
Cohen
E P
EP
Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Molteni
A
A
Hill
P
P
Fish
B L
BL
Ward
W F
WF
Moulder
J E
JE
Carone
F A
FA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000528:radiation effects; D001160:Arterioles / Q000187:drug effects / Q000528:radiation effects; D002216:Captopril / Q000494:pharmacology*; D004396:Coloring Agents; D006651:Histocytochemistry; D007668:Kidney / Q000503:physiopathology* / Q000648:ultrastructure*; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D011833:Radiation Injuries, Experimental; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects / Q000528:radiation effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004396:Coloring Agents; D002216:Captopril