Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity
Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO...
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Veröffentlicht in: | Nature medicine 2007-02, Vol.13 (2), p.189-197 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO
•
). Here we show that aldosterone (10
−9
–;10
−7
mol/l) decreased endothelial G6PD expression and activity
in vitro
, resulting in increased oxidant stress and decreased NO
•
levels—similar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP−response element modulator (CREM) to inhibit cyclic AMP−response element binding protein (CREB)-mediated
G6PD
transcription.
In vivo
, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity. These effects were abrogated by spironolactone or vascular gene transfer of
G6pd
. These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of
G6pd
improves vascular reactivity by restoring G6PD activity. |
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ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/nm1545 |