1 dose of endotoxin causes endothelial dysfunction for up to 1 week

[Mauritio]

In this study they injected endotoxin into the hand of healthy volunteers.
As it turned out, one dose of endotoxin lead to persistent constriction of the blood vessel that took up to 1 week to recover!

There's molecules like nitric oxide, serotonin , bradikinin ,arachidonic acid or CO2 that dilate the blood vessels in general .

So to test the dilation ability they injected bradikinin or arachidonic acid (both raise NO) shortly after endotoxin exposure.
Both failed to relaxed the endothelium and it took a week to fully recover that ability.

I don't know why the blood vessels endothelium takes such a long time to recover their ability to relax after endotoxin exposure.
But that might explain why some individuals in later stages of their life or in bad health (high endotoxin) don't even respond to viagra anymore: the constant endotoxin exposure makes them "immune" to nitric oxid's vasodilation and causes "endothelial stunning" as the authors called it.

Maybe the endotoxin lowers CO2 too much . So there's no proper relaxation possible anymore.

I originally stumbled upon this ,because i think there's a connection between endotoxin and varicose veins . But wouldn't varicose veins have too much dilation and therefore profit from endotoxins constriction ?

(Endothelial "stunning" following a brief exposure to endotoxin: a mechanism to link infection and infarction? - PubMed)

 

[Lollipop2]

Interesting find. Following.

 

[yerrag]

I don't know about endotoxins as well as about bacteria, but with internal bacterial infection in blood vessels, lately my experience has been that mitochondrial respiration is downregulated in order to use direct glucose metabolism toward the PPP pathway, so that more NADPH enzymes can be produced, so that the mitochondria can produce more ROS, which are needed in phagotyzing bacteria.

I think that endotoxins may still be phagocytized but it may involve not just neutrophils but also macrophages, or maybe neutrophils are much less involved.

But in downregulating oxphos, less CO2 would be generated, and if the situation stays long enough, CO2 would run low. I personally see my urine turn gradually more alkaline each time I wake up to pee, such that by the time I'm near wakeup, I would be snoring, as my sleep app would record my snore.

The reason for the snore is low CO2 leading to poor tissue oxygenation. The body responds by increasing breathing, but not to expel CO2, but to try to take in more oxygen-which really doesn't help.

At this point, I couldn't sleep anymore as in waking up my body goes back into oxphos mode, away from PPP, and gradually my blood CO2 content is regained.

While awake, I think PPP is downregulated, and this would explain why I would urinate more at night and less in the daytime. At night, more ROS produced and spilled over, more oxidative stress that is balanced by endogenous antioxidants, and since this is a redox reaction, water is produced - lots of it. And that's why I would urinate more at night.

Sorry, I am commenting without reading the study. A lot of times, I find studies to be limited in giving the whole story. I liken many times to CNN news reporting where they capture a part of what Trump says, to brazenly put it out of context.

For the money or funding or to keep the job. Context is the victim oftentimes.

 

[Mauritio]

Sorry, I am commenting without reading the study.

Yeah, I was like: "what has all of this to do with this study? "

Although the first paragraph is somewhat applicable to this study. So getting rid of the infection might increase vascular health.

Do you have any knowledge on the bacteria/endotoxin - varicose vein connection ?

 

[yerrag]

Yeah, I was like: "what has all of this to do with this study? "

Although the first paragraph is somewhat applicable to this study. So getting rid of the infection might increase vascular health.

Do you have any knowledge on the bacteria/endotoxin - varicose vein connection ?

Just as any muscle, as the endothelial lining is considered a smooth muscle, it takes energy for it even just to relax. And since the endotoxins are a source of inflammation, I think resources for energy production are being channeled towards immune reactions to resolve that inflammation. There is less energy available to effect the contraction of the endothelial lining. The body sees the endotoxins and its inflammatory effects to be a more immediate concern, and uses its resources towards eliminating this threat, at the expense of providing energy for the regular relaxation of the blood vessels. Until the inflammation, s resolved (as endotoxins are harder to put away), the blood vessels may not be able to contract and relax normally. Using vasodilators don't help, as it is an energy issue.

That is the best explanation I can come up with. I hope it makes sense.

 

[Jing]

How do we make sure we don't have any endotoxin?

 

[Razvan]

How do we make sure we don't have any endotoxin?

No starch. Calcium and B3.

 

[Jing]

No starch. Calcium and B3.

H
Thanks, How much calcium and b3 ?

 

[Mauritio]

How do we make sure we don't have any endotoxin?

There's a ton of ways . TLR4 antagonists, anti-biotocs , keeping speed time high .
Just making sure you dont have too many microbes down there and eat foods that you tolerate well is important . Easier said than done though!