EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION ON GLOMERULAR CAPILLARY WALL ULTRASTRUCTURE IN MWF ZTM RATS/

Previous studies have documented that treatment with angiotensin-conve rting enzyme (ACE) inhibitors prevents spontaneous proteinuria and enh ances the glomerular ultrafiltration coefficient in male MWF/Ztm rats. The aim of this study was to study whether these beneficial effects o f ACE inhibitors on glomerular capillary wall function are derived fro m 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 tre ated with the ACE inhibitor cilazapril for 2 and 6 months and in age-m atched untreated controls. At the end of the observation periods, both systolic blood pressure and urinary protein excretion were significan tly reduced in treated animals as compared with controls. Glomerular v olume increased significantly with time but was comparable in control and in treated rats. Surface area available for filtration (measured a s 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 sign ificant ultrastructural changes such as basement membrane thickness, c onfiguration of epithelial podocytes, and the width and the frequency of the epithelial slit diaphragms. These results indicate that the pre viously observed increase in the glomerular ultrafiltration coefficien t by an ACE inhibitor in these animals is not the consequence of chang es in filtering surface area but likely reflects an increase in membra ne hydraulic permeability. Changes in glomerular basement membrane and in the frequency of the epithelial slit pores cannot explain the amel ioration of glomerular permeability to water and macromolecules induce d by the treatment. The beneficial effects induced by the inhibition o f angiotensin on capillary wall function might be related to mesangial volume expansion.