The NO/ONOO cycle - disrupted endothelial caveolae?

Given the focus on endothelial dysfunction (read previous posts) perhaps it is time to take another look at Martin Palls old hypothesis about the NO/ONOO^-  cycle:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a NO/ONOO- Cycle Disease

Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO– cycle

Martin Palls NO/ONOO- cyklus (på dansk/in Danish)

And his latest paper:

The NO/ONOO-Cycle as the Central Cause of Heart Failure

..if there is a peroxynitrite (ONOO- ) problem in ME/CFS – do ME/CFS patients have disrupted endothelial caveolae – as in this paper?

Peroxynitrite Disrupts Endothelial Caveolae Leading to eNOS Uncoupling and Diminished Flow-Mediated Dilation in Coronary Arterioles of Diabetic Patients:

• Peroxynitrite (ONOO^- ) contributes to coronary microvascular dysfunction in diabetes mellitus (DM).
• NO-mediated coronary flow-mediated dilatation (FMD) was significantly reduced in DM patients, which was restored by ONOO^-  scavenger.
• The researchers propose, that ONOO^-  selectively targets and disrupts endothelial caveolae, which contributes to NO synthase uncoupling, hence reduced NO-mediated coronary vasodilation in DM patients.

…and may an ONOO^-  scavenger help ME/CFS patients?

(Remember: Flow-mediated dilatation (FMD) is a test for assessing endothelial dysfunction, and a study, Large and small artery endothelial dysfunction in chronic fatigue syndrome, showed FMD was significantly lower in ME/CFS patients.)

Some ME/CFS patients say vitamin B12 (cobalamin) helps, and others say it makes no difference. I do not know what to believe, but something I do know, is that the biochemistry behind this is very complicated. I found this paper: 

The return of the Scarlet Pimpernel: cobalamin in inflammation II - cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS

And then there is folic acid and eNOS activity: 

Folic acid modulates eNOS activity via effects on posttranslational modifications and protein–protein interactions

Folic Acid Reverts Dysfunction of Endothelial Nitric Oxide Synthase

And what about vitamin C - can it enhance nitric oxide bioavailability?:

Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? In vitro, in vivo and clinical studies

...I fear that vitamins alone can't fix the broken cycle in ME/CFS, but let us hang in there and follow the research about it!!! 

I do believe we are getting closer to answers and a treatment!