Conclusions/interpretation
Increased oxidative stress induces glomerular ESL deterioration in part through increased heparanase levels, resulting in exacerbation of glomerular permselectivity and development of albuminuria.
Methods
Male Zucker fatty (ZF) rats with albuminuria and Zucker lean (ZL) rats were used in this study. Some of the ZF rats were treated with the angiotensin II receptor blocker, irbesartan. We determined the amount of ESL by wheat germ agglutinin staining and heparan sulphate proteoglycan production by western blot analysis. Glomerular hyperfiltration of macromolecules was visualised using in vivo microscopy. We used 2',7'-dichlorofluorescein diacetate-derived chemiluminescence staining to assess ROS production, and heparanase production and expression were determined by western blot analysis and quantitative real-time polymerase chain reaction respectively.
Results
By 18 weeks of age, ZF rats had developed albuminuria. The glomerular endothelial cell glycocalyx was significantly decreased in ZF compared with ZL rats. Glomerular filtration and the permeability of macromolecules were increased in ZF, but not in ZL rats. Glomerular ROS and heparanase production were significantly increased in ZF compared with ZL rats. These changes in ZF rats were reversed by irbesartan treatment. Conclusions/interpretation: Increased oxidative stress induces glomerular ESL deterioration in part through increased heparanase levels, resulting in exacerbation of glomerular permselectivity and development of albuminuria.