Effects of delayed treatment with enalapril and/or lovastatin on the progression of glomerulosclerosis in 5/6 nephrectomized rats.

To evaluate the effect of delayed treatment with enalapril or lovastatin on the progression of glomerulosclerosis and to examine if the combined treatment with enalapril and lovastatin show synergistic effect, a total of 31 Sprague-Dawley rats were studied for 16 weeks following 5/6 nephrectomy (NPX). Treatment was delayed until 8 weeks after NPX. In untreated control rats (n = 8), sustained systemic hypertension with increasing proteinuria, serum cholesterol, triglyceride, BUN and widespread glomerulosclerosis and mesangial expansion were observed. Treatment with enalapril alone (R, n = 8) reversed systemic hypertension, prevented a further increase in proteinuria, and significantly reduced glomerulosclerosis relative to the control group. Treatment with lovastatin alone (L, n = 7) also reduced glomerulosclerosis and serum cholesterol compared to the controls. The drug also prevented a further increase in proteinuria and systemic blood pressure although the difference from the control rats did not reach statistical significance. Treatment with both enalapril and lovastatin (RL, n = 8) almost completely prevented glomerulosclerosis and significantly reduced mesangial expansion, systemic blood pressure, serum cholesterol, and proteinuria compared to controls. Only the combined treatment stabilized BUN and reduced mesangial expansion compared to control R, or L groups. Conclusion. Delayed treatment with enalapril or lovastatin is effective in preventing the progression of glomerulosclerosis, and combined treatment appears to show synergistic effect in 5/6 nephrectomized rat model.