Article
ACE inhibition normalizes altered expression patterns of ROS generating genes in glomerular proteinuria
ACE-Inhibition normalisiert veränderte Expressionsmuster ROS-bildender Gene in der glomerulären Proteinurie
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Published: | November 11, 2004 |
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Proteinuria and hypertension are the most important factors for the progression of renal disease and the development of terminal renal failure. To study the role of oxidative stress and reactive oxygen species (ROS) in the glomerulus we performed systematic expression analysis in the Munich Wistar Frömter rat (MWF). The MWF strain represents a suitable genetic model for increased albuminuria (proteinuria) and spontaneous arterial hypertension. We determined the expression of the NADPH subunits NOX1, NOX4, p22-phox, p47-phox, and rac1 as well as eNOS and iNOS in glomerular RNA with the TaqMan technique. All measurements were carried out in three groups consisting of untreated MWF, untreated Wistar control rats, and ACE-inhibitor (ACE-I) treated (between week 16 and 24 of age) MWF rats (n=8-12, respectively). Systolic blood pressure of unreated MWF (168 +- 3 mm Hg p<0.005 vs. Wis ) was normalized by ACE-I (129 +- 2 mm Hg) to normotensive Wis control levels (127 +- 2 mm Hg). ACE-I treatment was able to stop the progression of albuminuria in MWF, while no reversion to normal levels was observed. No change in expression between the three groups could be observed for the NOX1, NOX4, p22-phox, and rac1 genes, respectively. The cytosolic subunit p47-phox, however, was clearly elevated (2.3 fold, p<0.05 vs. Wis) in untreated MWF rats and its expression could be normalized by ACE-I treatment. NO synthase isoforms eNOS and iNOS showed a significant upregulation of in untreated MWF rats (199.4 +- 52.1 % and 243.5 +- 99.5 %, respectively; p<0.05 vs. Wis), whereas the ACE-I-treated group exhibited no difference in eNOS and iNOS levels compared to the healthy Wistar control rats. Our data hint towards an imbalanced expression of ROS-generating genes as well as eNOS and iNOS in the glomerulus of MWF, which is normalized by ACE-I treatment.