The effect of enalapril on glomerular growth and glomerular lesions after subtotal nephrectomy in the rat: a stereological analysis

Abstract

Introduction: Angiotensin converting enzyme (ACE) inhibitors have a beneficial effect on glomerular injury in different models of renal damage. Their presumed nephroprotective action has been related partly to actions on glomerular growth. We examined the effect of prophylactic administration of a moderate dose of enalapril (50 mg/l in drinking water) in male Sprague-Dawley rats on a diet containing 40% protein and moderate NaCl.

Methods: The rats were followed for 8 weeks after subtotal nephrectomy and compared with sham-operated matched controls.

Results: The number of glomeruli per kidney was reduced significantly in both the enalapril-treated and control groups. The median glomerulosclerosis index was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The mean absolute glomerular volume was significantly higher after subtotal nephrectomy, but was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The total numbers of cells per glomerulus and of mesangial or endothelial cells, as well as nuclear volumes of mesangial cells and the total capillary length per glomerulus, were all significantly higher after subtotal nephrectomy. These parameters were significantly lower in the enalapril-treated than in the untreated nephrectomized rats. The rise in systemic blood pressure was modest in the nephrectomized rats and the arteriolar volume: length ratio was unchanged by treatment with enalapril.

Conclusions: In subtotally nephrectomized rats enalapril inhibits (but fails to reverse completely) the compensatory glomerular enlargement and the increase in mesangial cell number and activation, with a concomitant reduction in the development of glomerulosclerosis. The results is compatible with antiproliferative, and possibly antiangiogenic, actions of ACE inhibitors.