Long-term enalapril and verapamil in rats with reduced renal mass

Abstract

The effect of long-term treatment with either enalapril or high dose verapamil on survival, proteinuria, blood pressure and renal morphology was studied in female Wistar rats with markedly reduced renal mass. Four weeks were allowed for remnant kidney hypertrophy before determining the response to renal ablation of individual animals regarding proteinuria and hypertension. At this time, five groups of 18 rats were formed with equal levels of proteinuria and hypertension. Groups E1 and E2 were treated with enalapril, groups V1 and V2 with verapamil, and one group served as control. The daily food allowance was 14 g/rat of a standard rat diet, containing 30% protein and 100 mmol NaCl/kg food in groups E1 and V1. NaCl content was reduced to 20 mmol/kg food in groups E2, V2 and control. The drugs were added to the drinking water, enalapril at a dose of 0.1 g/liter, verapamil at 0.5 to 0.7 g/liter. Drug intake thus amounted to 10 to 25 mg/kg for enalapril and 50 to 140 mg/kg for verapamil. Treatment was continued for 15 weeks. Three of the 18 control rats did not survive up to 15 weeks. Mortality was lower in the enalapril treated groups with a single nonsurvivor in group E1. In contrast, mortality was higher in the verapamil treated animals with seven nonsurvivors in group V1 and eight in group V2. Blood pressure control was excellent in both enalapril treated groups, and proteinuria decreased in most animals of group E1 and all of group E2. Glomerulosclerosis did not develop in the majority of the enalapril treated animals. Despite the high dose, verapamil barely lowered blood pressure. However, proteinuria rose markedly in response to verapamil causing hypoalbuminemia and hyperlipidemia. Increased proteinuria was associated with a higher percentage of sclerotic glomeruli in the verapamil treated groups. Kidney weight was highly significantly correlated with proteinuria. Kidney enlargement thus appeared to be caused by tubular dilatation and filling with proteinaceous casts depending on the level of proteinuria. The favorable effect of enalapril on remnant kidney function and morphology was confirmed. In contrast, verapamil worsened proteinuria, tended to promote glomerulosclerosis and shortened survival of rats with reduced renal mass.