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Title:
Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity | Nature Medicine
Description:
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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nature portfolio permissions reprints privacy policy advertising nature glucose-6-phosphate dehydrogenase activity cyclic amp-mediated upregulation social media glucose-6-phosphate dehydrogenase gene glucose-6-phosphate dehydrogenase g6pd-deficient endothelial cells methylenetetrahydrofolate reductase-deficient mice angiotensin ii-dependent pathway article initially published aldosterone-induced inflammation aldosterone synthase-transgenic mice suppresses vascular angiotensin author correspondence modulates vascular function limiting oxidant stress springerlink instant access permissions mediated g6pd transcription impaired vascular reactivity high-salt diet camp-mediated repression increased oxidant stress g6pd-deficient phenotype aldosterone-induced vasculopathy endothelial cell lines personal data aortic endothelial cells restoring g6pd activity european economic area large artery compliance privacy aldosterone-treated cells vascular gene transfer programmed cell death data protection data interpretation impair endothelial function vascular response increasing g6pdh expression issue learn harvard medical school downstream transcription factors explore content subscription content /angiotensin ii conversion
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headline:Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity
description: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 (NOâ¢). Here we show that aldosterone (10â9â;10â7 mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO⢠levelsâsimilar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMPâresponse element modulator (CREM) to inhibit cyclic AMPâresponse 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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headline:Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity
description: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 (NOâ¢). Here we show that aldosterone (10â9â;10â7 mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO⢠levelsâsimilar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMPâresponse element modulator (CREM) to inhibit cyclic AMPâresponse 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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name:Boston University School of Medicine, Boston, USA
name:Whitaker Cardiovascular Institute
name:Boston University School of Medicine, Boston, USA
name:Whitaker Cardiovascular Institute
name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
name:Boston University School of Medicine, Boston, USA
name:Whitaker Cardiovascular Institute
name:Boston University School of Medicine, Boston, USA
name:Whitaker Cardiovascular Institute
name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
name:Boston University School of Medicine, Boston, USA
name:Whitaker Cardiovascular Institute
name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
name:Boston University School of Medicine, Boston, USA
name:Renal Section, Joslin Diabetes Center, 1 Joslin Place, Harvard Medical School, Boston, USA
name:Division of Cardiology, University of Michigan School of Medicine, Taubman Medical Center, Ann Arbor, USA
name:Whitaker Cardiovascular Institute
name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
name:Boston University School of Medicine, Boston, USA
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