Angiotensin-converting enzyme inhibition prevents loss of glomerular hydraulic permeability in passive heymann nephritis

We used morphometric techniques and theoretical analysis to investigate str uctural and functional changes of the glomerular membrane that develop in p assive Heymann nephritis (PHN), an experimental model of human membranous g lomerulopathy. The effect of angiotensin-converting enzyme (ACE) inhibition on the above parameters was also investigated to explore the mechanisms by which this treatment exerts functional and structural protection at the re nal tissue level. Morphometric analysis of glomerular capillary by light an d electron microscopy was performed in normal control rats and in rats inje cted with rabbit anti-Fx 1A antibody, 12 months after induction of PHN. A g roup of PHN rats treated with lisinopril during the observation period was also investigated. Glomerular capillary architecture was not significantly altered in PHN rats, thus glomerular volume and capillary lumen volume were comparable with normal controls; only mesangial volume was significantly e levated in PHN rats. Glomerular membrane structure was significantly affect ed by PHN: the thickness of the glomerular basement membrane (GBM) increase d, and the frequency of epithelial filtration slits decreased. Electron-den se deposits in the subepithelial space of the GBM were estimated to occupy more than 20% of the GBM area. Theoretical analysis of glomerular hydraulic permeability allowed us to predict that, after these structural changes, t he permeability of the GBM and the epithelial layer significantly decreased , with an average reduction in the ultrafiltration coefficient (K-f) of app roximately 43%. ACE inhibition limited mesangial expansion and prevented ch anges of glomerular epithelial cells (filtration slit frequency) but not GB M thickening. Immune deposits within the GBM were only partially prevented by lisinopril. A selective effect on epithelial permeability was calculated in lisinopril-treated rats, and a partial preservation of K-f reduction wa s observed. These results suggest that structural changes of the GBM and ep ithelial cells that develop in PHN are responsible for the reduced filtrati on capacity observed in this model. ACE inhibition only partially prevented immune-deposits in the GBM and favorably affected epithelial cell structur e. These selective effects on glomerular podocytes may contribute to preser ve water and macromolecule permeability of the glomerular capillary wall in this immunologic model of kidney disease.