The things a person would want to particularly talk with his or her doctor about, in relation to the vasodilatory effects of things like reduced folates, would be the presence of some kind of vascular disease or thrombogenic condition. For example, L-methylfolate can scavenge peroxynitrite at concentrations in the range of 1 uM, to a degree that was comparable to the effect of 1 uM uric acid in this study:
http://www.ncbi.nlm.nih.gov/pubmed/16940192
That effect would tend to protect against reperfusion injury or, in this case, issues. But the initial effect would be to dilate the blood vessels by increasing nitric oxide release from endothelial cells, and this could cause low-level reperfusion-induced inflammation or "issues" in a person with existing peripheral arterial disease (a generic category). Even aside from the reperfusion issues (as opposed to overt injury), an acute increase in nitric oxide levels is known to inhibit platelet function and could thereby cause bleeding in a vulnerable individual. Here's one article showing the inhibition of platelet function by nitric oxide (a fairly reliable effect, even though there tends to be tolerance to this effect):
http://www.ncbi.nlm.nih.gov/pubmed/9731013
The combination of a low-level antiplatelet effect of nitric oxide and vasodilation, by whatever mechanisms, could potentially be bad, in the short term, in some people. Even though many things that enhance nitric oxide bioavailability and produce vasodilation protect against reperfusion injury, this is not always true (especially when there's some kind of thrombogenic tendency).
This is an extreme example of reperfusion injury, and these effects are not likely to occur with something like a reduced folate. I guess it's in some obscure journal, but there are countless, similar case reports. But in this extreme example, a person had surgery to restore blood flow to one leg. After the surgery, the person's leg swelled up, because of reperfusion-induced rhabdomyolysis (lysis of muscle cells). The person died of renal failure and, secondarily, multiple organ failure from the accumulation of myoglobin and other muscle-derived proteins in the kidneys (via the blood). Myoglobinuria is a major mechanism of renal failure due to rhabdomyolysis. But the point is that sudden vasodilation can produce reperfusion injuries, under some conditions (such as an existing thrombogenic condition, etc.), and the increased tissue oxygenation, resulting from the increase in blood flow, can cause very severe "free-radical" damage that far outweighs any benefit, in the short term, that might come from the restoration of blood flow. In any case, it's worthwhile for a person and his or her doctor to be aware of the range of mechanisms and the short-term vs. long-term mechanisms:
http://www.tsoc.org.tw/db/Jour/1/200404/17.pdf
No comments:
Post a Comment