(MY BOLDING)And then maybe we come back to the same question - what causes the vascular dysfunction? I had been thinking about this particular spaghetti loop and had come to think that at least for MEs the problem is unlikely to START in the autonomic nervous system. The reason for this is that we seem to be dealing with a re-setting of some complex regulatory system. The immune system and the brain are complex enough to reset themselves to a new level through confused internal loops. My guess is that the autonomic nervous system is not quite that complicated - it works like the control system on your central heating and is quite complicated but it may not be complicated enough to reprogramme itself - if that makes sense. Somebody else is re-programming it. You might say that hypertension is a resetting of the autonomic system but I am pretty sure that the real causes of hypertension lie outside and that the autonomic system just resets the way it usually does - although in this case unhelpfully. This may be a confused analysis but it is as far as I have got so far!
There is a concept in complex systems theory, chaos theory, and catastrophe theory, that these are dynamic stable states drawn to a strange attractor. A strange attractor is a central tendency, the "fixed point" around which the system revolves, but the system is more chaotic and fractal than stable. What happens in some situations is the system becomes highly perturbed. Then it becomes fully unstable, and then resettles back to the strange attractor. Except sometimes the attractor changes, leading to a new stable state that is different from before.
I first came across this in ME from the work of Dr Andriya Martinovic, circa 1993, in connection with eicosanoid regulation in ME/CFS (he used the Holmes criteria mostly). Earlier I was interested in this from the perspective of neural modelling, which I was working on for my PhD candidacy (which ended when I found I could no longer read or even count to 3).
The point is that homeostatic mechanisms are in part from internal settings, and in part from external and internal communication. If its perturbed enough the homeostatic balance can alter. This is less like a thermostat than it is an ecology ... the ecology can find a new balance, but its not the same ecology.
Teasing this situation apart from a causal tangle is difficult, and you always have the possibility that one or more constant external factors are driving the perturbations. That is why we need to untangle the mess, identify key pathways, and then start to think about the dynamics of how it all fits together. The problem is that complex dynamic systems in the real world (and not artificial models) are still largely beyond precise scientific understanding.
That is why basic research is so important. We will never know which study could provide that last vital clue we need until maybe even years after it is done. With so little research into ME biology, relying on serendipity is very problematic.