Effects of angiotensin-converting enzyme inhibition on glomerular capillary wall ultrastructure in MWF/Ztm rats

Previous studies have documented that treatment with angiotensin-converting enzyme (ACE) inhibitors prevents spontaneous proteinuria and enhances the glomerular ultrafiltration coefficient in male MWF/Ztm rats. The aim of this study was to study whether these beneficial effects of ACE inhibitors on glomerular capillary wall function are derived from the preservation of its ultrastructure. Conventional morphometrical analysis of kidney tissue, by light and electron microscopy, was used to quantify glomerular structural changes in the male MWF/Ztm rats treated with the ACE inhibitor cilazapril for 2 and 6 months and in age-matched untreated controls. At the end of the observation periods, both systolic blood pressure and urinary protein excretion were significantly reduced in treated animals as compared with controls. Glomerular volume increased significantly with time but was comparable in control and in treated rats. Surface area available for filtration (measured as peripheral capillary wall) was comparable in control and in treated animals at the same time and increased significantly with time only in treated rats. Mesangial volume was significantly higher in cilazapril-treated animals than in controls after 2 months of treatment and was comparable after 6 months. ACE inhibitor treatment did not induce significant ultrastructural changes such as basement membrane thickness, configuration of epithelial podocytes, and the width and the frequency of the epithelial slit diaphragms. These results indicate that the previously observed increase in the glomerular ultrafiltration coefficient by an ACE inhibitor in these animals is not the consequence of changes in filtering surface area but likely reflects an increase in membrane hydraulic permeability. Changes in glomerular basement membrane and in the frequency of the epithelial slit pores cannot explain the amelioration of glomerular permeability to water and macromolecules induced by the treatment. The beneficial effects induced by the inhibition of angiotensin on capillary wall function might be related to mesangial volume expansion.