Ok...will try to explain better.
I'm certainly not a chemistry expert, 1 eye, but have been reading papers on NO for seven years now, trying to get a handle on endothelial dysfunction. eNOS has been my focus. Dr. John Cooke, author of The Cardiovascular Cure, has been my mentor/go to expert in this understanding, because I was looking at the vascular connection to MS--as evidenced by Jeff's serum numbers and hypercoagulation, etc. I was looking at ways to reverse endothelial dysfunction via eNOS. Oxidative stress and hypercoagulation were addressed in The Endothelial Health program:http://ccsvi.org/index.php/helping-myse ... ial-health
Despite the generation of NO by the oxygen-independent conversion of nitrate and nitrite, there are three major enzyme isoforms producing the molecule. These so-called NO synthases (NOS) utilize L-arginine and molecular oxygen to provide the free radical gas NO.
Neuronal NOS (nNOS or NOS1) was the first discovered isoform. nNOS is not only specific for neurons, but was also detected in other cell types, such as cardiomyocytes and arterial smooth muscle cells.[12,13] Inducible NOS (iNOS or NOS2) was originally isolated from macrophages and is expressed in glial cells. Endothelial NOS (eNOS; NOS3) was also found in neurons. Recently, mitochondrial NOS (mtNOS, NOS4) was detected in the inner mitochondrial membrane of different tissues such as brain, liver and heart. mtNOS seems to modulate redox status and is involved in brain development.
As in all biological systems, detrimental and/or beneficial effects of a molecule depend on its concentration in the microenvironment, resulting in either physiological or pathological processes. eNOS, as well as nNOS, are regulated by changes in intracellular calcium and by direct phosphorylation, producing only nanomolar levels of NO. By contrast, iNOS is induced independently of intracellular calcium by proinflammatory cytokines, leading to excessive NO release. Generally, the enzyme activity of iNOS is not enhanced compared with nNOS and eNOS, but increased iNOS protein can transiently be induced.
Again, I focused on eNOS to help Jeff's health, so that's what I know most about.
Why eNOS is important in vascular health:http://circ.ahajournals.org/content/113/13/1708.full
How eNOS is released by the sun's UV rays, into our skin and circulatory systems via dietary nitrates stored in our flesh--
Dr. Richard Weller is the expert studying this mechanism.http://www.nature.com/jid/journal/v134/ ... 1427a.html
Here's a 10 minute TED talk that explains it in (witty) layman's terms:https://www.ted.com/talks/richard_welle ... anguage=en
How eNOS is released by exercise:http://www.sciencedaily.com/releases/20 ... 103948.htm
How eNOS is activated by dietary isoflavones:http://cardiovascres.oxfordjournals.org ... t/75/2/261
This is going to get convoluted, but hang on.
After a stroke, iNOS and nNOS are activated in the brain, because ischemia induces an overproduction of NO, which is damaging.But eNOS looks to be protective:
Indeed, in certain circumstances, NO confers protection against stroke because mice deficient in eNOS suffer greater damage than control mice after reversible ischemia (Huang et al., 1996). One explanation is that NO is not toxic in itself but becomes toxic only when it reacts with superoxide and is converted to peroxynitrite (Beckman and Koppenol, 1996) and that the likelihood that this will occur is dependent on where NO is being produced.
Endothelial NO preserves collateral blood flow during ischemia, thereby reducing acute neuronal damage. Thrombocyte function is influenced by NO that is produced by endothelial cells and by platelet-derived NO. Therefore, targeting eNOS as a regulating molecule of vascular hemostasis could open new strategies for prophylactic and acute stroke treatment. Furthermore, eNOS-derived NO promotes angiogenesis as well as neurogenesis offering a tool to support post-stroke regeneration. In addition, inflammatory processes after cerebral ischemia are modulated by endothelial NO, but pro- and anti-inflammatory effects of eNOS have been described. With regard to this, more insights into the relation of eNOS to post-stroke inflammation are needed.
There are many reasons oxygen may be under utilized, as I said on the other thread. Brain injury, neuronal loss, mitochondrial disease, increased iNOS and nNOS making O2 unavailable....pick your mechanism. Dr. Ge is still trying to figure it out.
One challenge from the current data is to answer the question of what is exactly the underlying cause of the changes of Yv and CMRO2 in MS. Although NO hypothesis of competitive inhibition of oxygen uptake in mitochondrial respiratory process was proposed, we could not exclude the contribution from neuronal tissue loss or cell death, which had a decreased oxygen demand and decreased oxygen utilization, based on these imaging data
And Dr. Alexander had a lot of great points at ISNVD as to why NO wouldn't be the culprit...but too tired to add now....going for walk,