Recently we developed a model of CSA nephropathy in rats characterized by tubulointerstitial (TI) injury, macrophage infiltration, and progressive interstitial fibrosis (Kidney International 1995;47: 935). To examine the role of apoptosis and the mediators involved in this model, we treated rats for 5 weeks with CSA with or without L-NAME (to block NO), Losartan (to block AII type I receptor), or Hydralazine/Furosemide (H/F). CSA treated rats had increased apoptosis of tubular and interstitial cells as documented by PAS, propidium iodide, TUNEL, and electron microscopy when compared to vehicle treated controls. Macrophages containing apoptotic cells could be confirmed by TUNEL/ED-1 double-staining. Apoptosis (TUNEL) correlated with degree of fibrosis (r=0.50), and macrophages/mm2 (r=0.61). The effect of AII blockade and NO inhibition was also assessed. Table

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We conclude that CSA treatment is associated with a marked increase in apoptosis of tubular and interstitial cells, which may play a role in the progressive hypocellularity accompanying interstitial fibrosis. The apoptosis is partially dependent on AII, and is consistent with our prior observations that blocking AII lessens the development of fibrosis in these animals.