Effect of angiotensin-converting enzyme inhibition on glomerular basement membrane permeability and distribution of zonula occludens-1 in MWF rats

The mechanism(s) by which angiotensin-converting enzyme (ACE) inhibitors pr event glomerular membrane loss of permselective function is still not under stood. In male MWF rats, which develop spontaneous proteinuria with age, AC E inhibitors prevent proteinuria and increase glomerular ultrafiltration co efficient. These renoprotective effects are not associated with ultrastruct ural changes of capillary wall components, This study was undertaken to inv estigate whether ACE inhibitors modulate functional properties of glomerula r basement membrane (GBM) and/or of epithelial cells, both of which have be en suggested to play a role in the maintenance of the glomerular filtration barrier. The hydraulic and macromolecular permeability of the GBM were det ermined, by an in vitro filtration system, in untreated or lisinopril-treat ed rats and in Wistar rats taken as controls, By indirect immunofluorescenc e and immunoelectron microscopy, glomerular distribution of the tight junct ion protein zonula occludens-1 (ZO-1), a component of the slit diaphragm, w as also studied. Results document that spontaneous proteinuria in MWF rats develops without significant changes in the permeability of the GBM to wate r and albumin, or in the ultrastructure of the podocyte foot processes, but is associated with an important alteration in the distribution of ZO-1 at the glomerular level. Lisinopril, which prevented proteinuria, also prevent ed glomerular redistribution of the protein. Thus, renoprotective effects o f ACE inhibitors are not associated with changes in intrinsic functional pr operties of GBM, or ultrastructural changes of the epithelial cells, but ra ther with preservation of glomerular ZO-1 distribution and slit diaphragm f unction, which are essential for maintaining the filtration barrier.