ANGIOTENSIN-CONVERTING, ENZYME-INHIBITION REDUCES THE EFFECT OF BROMOETHYLAMINE-INDUCED PAPILLARY NECROSIS AND RENAL FIBROSIS

Rats injected with a single, 50-mg dose of bromoethylamine (BEA) devel oped papillary necrosis accompanied by severe interstitial fibrosis. A t 1 mo, the creatinine clearance de creased (control 0.66 versus BEA 0 .33 ml/min per 100 g body wt, P = 0.02), and the urine albumin-to-crea tinine ratio increased markedly (control 0.19 versus BEA 0.51, P = 0.0 2), In a group of animals given the angiotensin-converting enzyme inhi bitor enalapril (Enal; 100 mg/L) in their drinking water for 4 wk, beg inning 1 wk before BEA injection, creatinine clearance improved signif icantly (BEA 0.33 versus Enal + BEA 0.52 ml/min per 100 g body wt, P = 0.01) and albumin excretion fell to zero. Histologic examination reve aled an 88% decrease in the area of papillary necrosis and a decrease in the degree of interstitial fibrosis in the corticomedullary junctio n. To determine whether this was due to changes in urine flow rate ind uced by enalapril, a group of animals was injected with BEA, and enala pril at the above dose was begun 1 wk later, After 1 mo, the enalapril -treated animals showed the same improvement in creatinine clearance ( BEA 0.33 versus BEA + Enal 0.50 ml/min per 100 g body wt, P = 0.03) an d suppression of albumin excretion. The area of papillary necrosis was reduced by 67%. In the BEA animals treated with enalapril, ED-1-posit ive cells, alpha-smooth muscle actin, and transforming growth factor-b eta, were decreased compared with BEA alone. It is concluded that in t his model of papillary necrosis, enalapril protects renal function and decreases interstitial fibrosis mediated at least in part through an angiotensin II/bradykinin-dependent mechanism.