endothelin 1 - natural inhibitors

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endothelin 1 - natural inhibitors

Postby gibbledygook » Mon Oct 13, 2008 6:30 am

Here's some more reasons to have quercetin and green tea:

1: Am J Clin Nutr. 2008 Oct;88(4):1018-25. Links
Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men.Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD.
School of Medicine and Pharmacology and the School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, Western Australia.

BACKGROUND: Dietary flavonoids may improve endothelial function and ultimately lead to beneficial cardiovascular effects. OBJECTIVE: The objective was to assess whether pure dietary flavonoids can modulate nitric oxide and endothelin-1 production and thereby improve endothelial function. DESIGN: A randomized, placebo-controlled, crossover trial in 12 healthy men was conducted to compare the acute effects of the oral administration of 200 mg quercetin, (-)-epicatechin, or epigallocatechin gallate on nitric oxide, endothelin-1, and oxidative stress after nitric oxide production was assessed via the measurement of plasma S-nitrosothiols and plasma and urinary nitrite and nitrate concentrations. The effects on oxidative stress were assessed by measuring plasma and urinary F(2)-isoprostanes. Plasma and urinary concentrations of quercetin, (-)-epicatechin, and epigallocatechin gallate were measured to establish the absorption of these flavonoids. RESULTS: Relative to water (control), quercetin and (-)-epicatechin resulted in a significant increase in plasma S-nitrosothiols, plasma nitrite, and urinary nitrate concentrations (P < 0.05), but not in plasma nitrate or urinary nitrite. Epigallocatechin gallate did not alter any of the measures of nitric oxide production. Quercetin and (-)-epicatechin resulted in a significant reduction in plasma endothelin-1 concentration (P < 0.05), but only quercetin significantly decreased the urinary endothelin-1 concentration. None of the 3 treatments significantly changed plasma or urinary F(2)-isoprostane concentrations. Significant increases in the circulating concentrations of the 3 flavonoids were observed (P < 0.05) after the corresponding treatment. CONCLUSIONS: Dietary flavonoids, such as quercetin and (-)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.

PMID: 18842789 [PubMed - in process]

1: Peptides. 2008 Sep 16. [Epub ahead of print] Links
Regulation of glial inflammatory mediators synthesis: Possible role of endothelins.Filipovich T, Fleisher-Berkovich S.
Department of Clinical Pharmacology, Ben-Gurion University, P.O.B 653, Beer-Sheva 84105, Israel.

Endothelins are well known as modulators of inflammation in the periphery, but little is known about their possible role in brain inflammation. Stimulation of astrocyte prostaglandin, an inflammatory mediator, synthesis was shown so far only by endothelin 3 (ET-3). By contrast, several studies showed no change or slight decrease of basal nitric oxide synthesis after treatment of astrocytes with endothelin 1 (ET-1) and ET-3. However, a significant increase in astrocytic and microglial nitric oxide synthase (NOS) was observed after exposure to ET-1 and ET-3 in a model of forebrain ischaemia. Here we demonstrate that all three endothelins (ET-1, ET-2, ET-3) significantly enhanced the synthesis of prostaglandin E(2) and nitric oxide in glial cells. Each of the selective antagonists for ETA and ETB receptors (BQ123 and BQ788 respectively), significantly inhibited endothelins-induced production of both nitric oxide and prostaglandin E(2). These results suggest a regulatory mechanism of endothelins, interacting with both endothelin receptors, on glial inflammation. Therefore, inhibition of endothelin receptors may have a therapeutic potential in pathological conditions of the brain, when an uncontrolled inflammatory response is involved.

PMID: 18838093 [PubMed - as supplied by publisher]

Related ArticlesFunctional characterization and expression of endothelin receptors in rat carotid artery: involvement of nitric oxide, a vasodilator prostanoid and the opening of K+ channels in ETB-induced relaxation. [Br J Pharmacol. 2005] Expression of nitric oxide synthase isoforms in the thyroid gland: evidence for a role of nitric oxide in vascular control during goiter formation. [Endocrinology. 1995] ETA and ETB receptor antagonists synergistically increase extracellular endothelin-1 levels in primary rat astrocyte cultures. [Brain Res. 1998] Endothelin in the pulmonary circulation with special reference to hypoxic pulmonary vasoconstriction. [Scand Cardiovasc J Suppl. 1997] Endothelin and endothelin antagonists: pharmacology and clinical implications. [Agents Actions Suppl. 1995] » See all Related Articles...
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Postby cheerleader » Tue Oct 14, 2008 7:58 am

Thanks so much for this, Alex! (For those, like me, who are still learning their med-speak...the endothelium is the thin layer of cells lining blood vessels. A healthy endothelium allows for good blood flow and stops leakage of blood...of concern especially in the blood-brain barrier. Also important to regulate inflammation and transport white blood cells.)

We added quercetin and EGCG as supplements to Jeff's lunchtime routine for 2 weeks now. He now takes only 1/2 dose of provigil, and has become quite energetic....our garage and closets got cleaned out this weekend, and he's tackling the honey-do list! Still no new petechiae.

We really appreciate your research abilities, Alex!
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Re: endothelin 1 - natural inhibitors

Postby jimmylegs » Sun Nov 27, 2011 4:43 pm

2011 update: magnesium also combats endothelin-1 in these scenarios...

Effect of magnesium sulfate on plasma endothelin-1 levels in normal and preeclamptic pregnancies.

Action of magnesium sulfate in the treatment of preeclampsia-eclampsia
Stroke. 1989;20:1273-1275

Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials
http://eurheartj.oxfordjournals.org/con ... /1/6.short
"Chronic homocysteinaemia in humans is accompanied by increased endothelin-1 (ET-1) levels, which is the strongest vasoconstrictor in human vasculature."

Serum cobalamin, homocysteine, and methylmalonic acid concentrations ...
"Hyperhomocysteinemia, which is most strongly associated with low cobalamin concentrations, is also most common in elderly whites, whereas that associated with renal insufficiency is more common in blacks and Asian Americans.

don't know if this effect is 'portable'

Zinc deficiency further increases the enhanced expression of endothelin-1 in glomeruli of the obstructed kidney
http://www.nature.com/ki/journal/v58/n2 ... 1724a.html

will continue to scour for more helpful aids to endothelin supression :)
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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Re: endothelin 1 - natural inhibitors

Postby jackD » Sun Nov 27, 2011 10:02 pm

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