The mechanism(s) by which angiotensin-converting enzyme (ACE) inhibitors prevent glomerular membrane loss of permselective function is still not understood. In male MWF rats, which develop spontaneous proteinuria with age, ACE inhibitors prevent proteinuria and increase glomerular ultrafiltration coefficient. These renoprotective effects are not associated with ultrastructural changes of capillary wall components. This study was undertaken to investigate whether ACE inhibitors modulate functional properties of glomerular basement membrane (GBM) and/or of epithelial cells, both of which have been suggested to play a role in the maintenance of the glomerular filtration barrier. The hydraulic and macromolecular permeability of the GBM were determined, by an in vitro filtration system, in untreated or lisinopril-treated rats and in Wistar rats taken as controls. By indirect immunofluorescence and immunoelectron microscopy, glomerular distribution of the tight junction protein zonula occludens-1 (ZO-1), a component of the slit diaphragm, was also studied. Results document that spontaneous proteinuria in MWF rats develops without significant changes in the permeability of the GBM to water 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 prevented glomerular redistribution of the protein. Thus, renoprotective effects of ACE inhibitors are not associated with changes in intrinsic functional properties of GBM, or ultrastructural changes of the epithelial cells, but rather with preservation of glomerular ZO-1 distribution and slit diaphragm function, which are essential for maintaining the filtration barrier.
(2000). Effect of angiotensin-converting enzyme inhibition on glomerular basement membrane permeability and distribution of zonula occludens-1 in MWF rats [journal article - articolo]. In JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. Retrieved from http://hdl.handle.net/10446/204391
Effect of angiotensin-converting enzyme inhibition on glomerular basement membrane permeability and distribution of zonula occludens-1 in MWF rats
Remuzzi, Andrea
2000-01-01
Abstract
The mechanism(s) by which angiotensin-converting enzyme (ACE) inhibitors prevent glomerular membrane loss of permselective function is still not understood. In male MWF rats, which develop spontaneous proteinuria with age, ACE inhibitors prevent proteinuria and increase glomerular ultrafiltration coefficient. These renoprotective effects are not associated with ultrastructural changes of capillary wall components. This study was undertaken to investigate whether ACE inhibitors modulate functional properties of glomerular basement membrane (GBM) and/or of epithelial cells, both of which have been suggested to play a role in the maintenance of the glomerular filtration barrier. The hydraulic and macromolecular permeability of the GBM were determined, by an in vitro filtration system, in untreated or lisinopril-treated rats and in Wistar rats taken as controls. By indirect immunofluorescence and immunoelectron microscopy, glomerular distribution of the tight junction protein zonula occludens-1 (ZO-1), a component of the slit diaphragm, was also studied. Results document that spontaneous proteinuria in MWF rats develops without significant changes in the permeability of the GBM to water 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 prevented glomerular redistribution of the protein. Thus, renoprotective effects of ACE inhibitors are not associated with changes in intrinsic functional properties of GBM, or ultrastructural changes of the epithelial cells, but rather with preservation of glomerular ZO-1 distribution and slit diaphragm function, which are essential for maintaining the filtration barrier.File | Dimensione del file | Formato | |
---|---|---|---|
064 2000 Macconi D (JASN).pdf
Solo gestori di archivio
Versione:
publisher's version - versione editoriale
Licenza:
Licenza default Aisberg
Dimensione del file
786 kB
Formato
Adobe PDF
|
786 kB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
Aisberg ©2008 Servizi bibliotecari, Università degli studi di Bergamo | Terms of use/Condizioni di utilizzo