Aldosterone Impairs Vascular Reactivity By Decreasing Glucose-6-phosphate Dehydrogenase Activity

Drareg

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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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). 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
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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)-mediatedG6PD 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.

http://www.nature.com/nm/journal/v13/n2/abs/nm1545.html
 

yerrag

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This is interesting. This may provide a clue as to why I experience hypertension. I recently tested my serum aldosterone levels. The result, 24,4 ng/dL is higher than 15 ng/dL, which I believe to be the cutoff for optimal aldosterone levels. If this were true, then I have hyperaldosteronism. This could very well explain why decreased endothelial G6PD expression resulted in increased oxidant stress and decreased NO• levels. Decreased NO levels would make it difficult for my blood vessels to relax, or dilate, and this would lead to hypertension.

I should take a serum G6PD enzyme test to find out if I have a deficiency of this enzyme. If this were the case, I can try taking spironolactone to see if it would have the effect of lowering my blood pressure.

Thanks!
 
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yerrag

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@Hans this is an interesting angle on NO!
 

yerrag

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Indeed. Lowering aldosterone should be the focus instead of lowering ROS or boosting G6PD.

I'm taking plenty of salt to see if this works. Last night, I took 2 teaspoons of it. Just not sure how much to take of it but I'll take 2 teaspoons 2x a day for a week and see how this goes. Then I'll try spironolactone if it doesn't work.

I know my serum potassium is normal, so it doesn't seem consistent with hyperaldosteronism. So I'm not sure if I'm really high in aldosterone. I should probably have a G6PD test to see if the putative low NO is caused by G6PD deficiency.
 
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yerrag

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I'm taking plenty of salt to see if this works. Last night, I took 2 teaspoons of it. Just not sure how much to take of it but I'll take 2 teaspoons 2x a day for a week and see how this goes. Then I'll try spironolactone if it doesn't work.

I know my serum potassium is normal, so it doesn't seem consistent with hyperaldosteronism. So I'm not sure if I'm really high in aldosterone. I should probably have a G6PD test to see if the putative low NO is caused by G6PD deficiency.

I'm getting arrhythmia with the increased salt intake. That's the cue to stop the increased salt intake I guess.

I'll probably have to go with other methods like pregnenolone and progesterone, and probably dhea to balance it out. Have to read some threads here to get a better idea of going about it. I also have to find out if i really have high aldosterone or not, as there's no information about how to interpret my serum aldosterone values. My potassium level is normal also, so that makes the case for high aldosterone being less likely.
 

shine

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I'm getting arrhythmia with the increased salt intake. That's the cue to stop the increased salt intake I guess.

I'll probably have to go with other methods like pregnenolone and progesterone, and probably dhea to balance it out. Have to read some threads here to get a better idea of going about it. I also have to find out if i really have high aldosterone or not, as there's no information about how to interpret my serum aldosterone values. My potassium level is normal also, so that makes the case for high aldosterone being less likely.

Whenever I take 1-2mg of DHEA sublingually my blood vessels immediately relax and I can see them pop out. DHEA is known to ameliorate endothelial dysfunction.
 
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Effect of aldosterone and mineralocorticoid receptor blockade on vascular inflammation
Hylton V Joffe, Gail K Adler
Heart failure reviews 10 (1), 31-37, 2005
Aldosterone, the final product of the renin-angiotensin-aldosterone system, is classically viewed as a regulator of renal sodium and potassium handling, blood volume, and blood pressure. Recent studies suggest that aldosterone can cause microvascular damage, vascular inflammation, oxidative stress and endothelial dysfunction. In animal models, aldosterone-mediated vascular injury in the brain, heart, and kidneys leads to stroke, myocardial injury, and proteinuria. These effects may be modified by dietary salt intake; aldosterone-mediated vascular damage is increased in susceptible animals fed a high-salt diet compared to a low-salt diet despite lower plasma aldosterone levels on the high-salt diet. In humans, there is a growing literature supporting the adverse effects of aldosterone in heart failure, hypertension, left ventricular hypertrophy, and renal disease. Aldosterone receptor antagonists are beneficial even in patients on angiotensin converting enzyme inhibitors and attenuate aldosterone-mediated vascular injury by mechanisms that appear to be independent of changes in systolic blood pressure. This review focuses on the adverse effects of aldosterone on the vascular system and describes our current understanding of the underlying mechanisms for this injury.






Dietary salt intake is related to inflammation and albuminuria in primary hypertensive patients
R Yilmaz, H Akoglu, B Altun, T Yildirim, M Arici, Y Erdem
European Journal of Clinical Nutrition 66 (11), 1214, 2012
RESULTS:
Systolic and diastolic BP measurements of patients were similar in the three salt-intake groups. CRP and urinary albumin levels were significantly higher in high-salt-intake group compared with medium-and low-salt-intake groups (P= 0.0003 and P= 0.001, respectively). CRP was positively correlated with 24-h urinary sodium excretion (r= 0.28, P= 0.0008) and albuminuria, whereas albuminuria was positively correlated with 24-h urinary sodium excretion (r= 0.21, P= 0.0002). Multiple regression analysis revealed that urinary sodium excretion was an independent predictor of both CRP and albuminuria.
CONCLUSIONS:
These findings suggest that high salt intake is associated with enhanced inflammation and target organ damage reflected by increased albuminuria in treated hypertensive patients independent of any BP effect.
 

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