CAPTOPRIL PRESERVES FUNCTION AND ULTRASTRUCTURE IN EXPERIMENTAL RADIATION NEPHROPATHY

Captopril protects rat lung from radiation-induced pneumonitis and fib rosis and preserves function and survival in experimental radiation ne phropathy. This study determined the structural benefit of captopril u sed preventively in radiation nephropathy. Twenty-eight Wag/RijMCW rat s, 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 irr adiation, and the rats were killed at 20 weeks. Using light and electr on microscopy, kidneys of irradiated no-drug rats showed glomerular tu ft capsular adhesions and hyalinization, focal tubular necrosis, sever e interstitial fibrosis, and marked thickening and hyaline degeneratio n of the wall of interlobular arteries and arterioles, with intimal pr oliferation 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 inte rstitial damage was seen in irradiated, captopril-treated animals, wit h only mild focal tubular interstitial injury and fibrosis seen. alpha smooth muscle actin-positive cells, probably myofibroblasts, were enh anced in the irradiated kidneys, and this expression was reduced in a dose-related fashion by captopril. There was also reduction in the art eriolar wall thickening, luminal occlusion, and collagen deposition in captopril-treated animals. The presence of elastin was not affected b y 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 inju ry.