Renal effects of HMG-CoA reductase inhibition in a rat model of chronic inhibition of nitric oxide synthesis
Jazyk angličtina Země Švýcarsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
16899993
DOI
10.1159/000094988
PII: 94988
Knihovny.cz E-zdroje
- MeSH
- albuminurie farmakoterapie MeSH
- analýza rozptylu MeSH
- atorvastatin MeSH
- glomerulus patologie MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- hypertenze chemicky indukované prevence a kontrola MeSH
- kaveolin 1 metabolismus MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- kyseliny heptylové farmakologie MeSH
- modely u zvířat MeSH
- nemoci ledvin prevence a kontrola MeSH
- NG-nitroargininmethylester farmakologie MeSH
- oxid dusnatý nedostatek MeSH
- potkani Wistar MeSH
- pyrroly farmakologie MeSH
- rhoA protein vázající GTP metabolismus MeSH
- statiny farmakologie MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- atorvastatin MeSH
- Cav1 protein, rat MeSH Prohlížeč
- kaveolin 1 MeSH
- kyseliny heptylové MeSH
- NG-nitroargininmethylester MeSH
- oxid dusnatý MeSH
- pyrroly MeSH
- rhoA protein vázající GTP MeSH
- statiny MeSH
- vascular endothelial growth factor A, rat MeSH Prohlížeč
- vaskulární endoteliální růstový faktor A MeSH
BACKGROUND/AIMS: In addition to their lipid-lowering effects, HMG-CoA reductase inhibitors (statins) induce a variety of pleiotropic actions that have been recently studied in the area of cardiovascular and renal protection. In the present studies we sought to determine whether statins retain beneficial effects in the experimental model of NO deficiency achieved by chronic administration of a pressor dose of L-arginine analogue N-nitro-L-arginine-methyl ester (L-NAME). METHODS: To address this issue, blood pressure (BP), renal function (GFR), and albuminuria were determined in rats treated for 4 weeks with L-NAME, L-NAME + atorvastatin (ATO), and in untreated controls. In addition, renal cortical protein expression of caveolin 1 (CAV1), vascular endothelial growth factor (VEGF), and activity of RhoA were also determined. RESULTS: L-NAME administration resulted in sustained elevation of BP, decreased GFR, and in higher albuminuria as compared to control animals. Co-administration of ATO with L-NAME normalized albuminuria and prevented decreases in GFR in L-NAME rats without having an impact on pressor effects of L-NAME. CAV1 protein expression was similar in all groups of rats. In contrast, VEGF expression and RhoA activity was increased in L-NAME-treated animals, and normalized with co-administration of ATO. CONCLUSION: Treatment with ATO exerts early nephroprotective effects in the NO-deficient model of hypertension. These effects could be mediated by amelioration of VEGF expression and reduction of RhoA activity.
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