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Aldosterone Induces Oxidative Stress Via NADPH Oxidase and Downregulates the Endothelial NO Synthesase in Human Endothelial Cells
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A. Mohamed Taye   |
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Abstract: (1365 Views) |
| Aldosterone is traditionally viewed as a hormone regulating electrolyte and blood pressure homeostasis. Recent studies suggest that Aldo can cause microvascular damage, oxidative stress and endothelial dysfunction. However, its exact cellular mechanisms remain obscure. This study was undertaken to examine the effect of Aldo on superoxide production in human umbilical artery endothelial cells (HUAECs) . Moreover we attempted to investigate possible roles of NADPH oxiadse isoforms Nox2 and Nox4 as well as p47phox and p22phox subunits. In addition, we examine how Aldo regulates endothelial NO synthase [1] in these settings. HUAECs were incubated for 2h hours [2] with Aldo 10 –7 mol/L . NADPH oxidase expression and activity were estimated by lucigenin-enhanced chemiluminescence . Moreover, eNOS expression was also determined. The present results showed that stimulation of HUAECs with Aldo (10–7 mol/L) resulted in a significant upregulation in each of Nox2, p47 phox and p22 phox protein levels, whose effects were abolished by the mineralcorticod receptor antagonist spironolactone [3] . However, Aldo did not exhibit any significant change in Nox4 protein level. Functionally, these effect were reflected on increased oxidative stress markers as evidenced by increased NADPH oxidase activity and superoxide production in addition to 3-nitrotyrosine (3-NT). Aldo-induced increased in superoxide production and nitrosative stress were inhibited by Spiro. On the other hand, Aldo significantly inhibited eNOS protein expression and pretreatment with Spiro restored eNOS to normal level. Taken together, the present results demonstrate that Aldo induces oxidative ? nitrosative via MR receptor-mediated activation of the NADPH-oxidase isoform Nox2 and downregulates eNOS in HUAECs. |
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| Keywords: Aldo-oxidative stress-NADPH oxidase-endothelium |
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Full-Text [PDF 351 kb]
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Article Type: Research Article |
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