There are probably many feedback loops where the body can try to restore function with a sluggish NO synthesis. However this may lead to further issues. So currently I see the problem as potentially inadequate regulation of lower than normal NO production, or slower NO production, and so on. However its intriguing that this might explain low blood volume, which has already been mentioned here. It might also explain much older findings but I am not currently able to investigate this. See the work by Vance Spence in the early 2000s.
There are so many substances in blood and we keep finding new ones. If its a signalling molecule(/s) then it might require a major search effort, fractioning the blood via various methods to get more isolated samples with fewer substances so that other methods have a smaller range of substances to investigate. Alternatively if we can figure out the target of the signals we could work in reverse by using a purified sample to bind to whatever is in the blood.
They might have to test every single band to see if its the one. So the fastest way is to test subfractions, then fractionate the active one again and again, testing as they go. Alternatively, and not necessarily better, they can hypothesize a substance and test that. However even if its active it might not be the only active substance.
But NO is a vasodilator. This study suggests ME/CFS plasma reduces NO production. So the results appear to be inconsistent with increased vasodilation in pwME – unless I’ve misunderstood (which is very possible).
I’m way out of my depth here but, if there is something in the plasma that is affecting the function of cells (endothelial and/or PBMC), is it possible, or even likely, that the quantity of this substance, and therefore the size of its effect on cell function, could increase in response to exertion? Have any of the “something in the blood studies” compared the effect of plasma from the same individuals before and after exertion? If not, is this something that might be useful to test?
That is my current take as well. However decreased synthesis in isolated cells do not take into account the systemic effects, including autonomic regulation. Figuring out ways to test actual patients, having identified issues of concern in isolated samples, is important to figure out what is actually happening.
Yes, may not be vasoconstriction, might be failure to compensate for increased demand, such as in exercise. However I think its likely it may induce lower blood volume, via very slight vasoconstriction.
Many patients have tried arginine and other agents over the years, I don't recall ever hearing of major results. One thing we do not know is if arginine works properly in ME. We also do not know how the suppression works.
In my day to day life I think about my ME as my body having problems regulating various functions which impedes recovery from the most menial of tasks.
And we should know if the plasma is from patients in PEM or not, as there might be differences.
Another thing is that it could be a feedback loop, so that the cells themselves produce a signal after having been exposed to the substance. I want a before/after study! I seem to remember a Fukuda study that used CPET that measured heat shock proteins in pwME and controls, where pwME had a different response to exercise (heat shock proteins protect cells from various environmental stressors, so if they don't function cells can become more vulnerable to say heat).
