BENEFICIAL EFFECT OF THE LONG-TERM TREATMENT WITH THE COMBINATION OF AN ACE-INHIBITOR AND A CALCIUM-CHANNEL BLOCKER ON RENAL INJURY IN RATSWITH 5 6 NEPHRECTOMY/

The effects of the addition of a calcium channel blocker, verapamil (2 0 mg/kg/day) to an ACE inhibitor, trandolapril (0.7 mg/kg/day) in a 6- month treatment on renal insufficiency development in rats with 5/6th nephrectomy, were studied. Every month we measured heart rate and arte rial pressure by the tail-cuff method. Renal function studies were per formed in metabolic cages. At the end of the study, renal tissue was p repared for light microscope analysis. Renal lesions were assessed by semiquantitative scores in a blind fashion. Corpuscular section area, intraglomerular and tubulointerstitial fibrosis were determined by dig ital image analysis with a specific software (Fibrosis HR(R)) on syriu m red-stained renal sections. Trandolapril markedly increased the surv ival ratio that after 6 months reached 87% in comparison with 61% in u ntreated rats. No mortality was observed in rats treated with the comb ination of verapamil and trandolapril. Trandolapril treatment prevente d the development of hypertension. The combination verapamil-trandolap ril did not induce further reduction on blood pressure. The untreated group showed a marked proteinuria, that in the trandolapril group show ed an important reduction. The verapamil + trandolapril group showed a proteinuria significantly smaller than that of all the other groups. Light microscopy semiquantitative studies of the renal injury showed t hat the trandolapril and verapamil + trandolapril groups had a marked reduction in glomerular and tubulointerstitial alterations, compared w ith untreated animals. Quantitative determinations of glomerular and i nterstitial fibrosis performed on syrium red-stained renal sections de monstrated that fibrosis was reduced when rats when treated with trand olapril and even more with verapamil + trandolapril when they were com pared to untreated animals' values. In conclusion, long-term treatment with verapamil given in addition to trandolapril produces additional protection against progressive renal injury associated to subtotal nep hrectomy.