People with cardiovascular disease produce lower than normal levels of nitric oxide that may account for decreases in blood flow and a decreased capacity of blood vessels to dilate. Now we know that even the low amounts of NO produced are tightly bound to glycosylated hemoglobin. Not surprisingly, when HbA1c is elevated, the NO that is present in red blood cells is not easily released to promote vasodilation. This may account, in part, for very low blood flow to the nerves of the feet and, thus to the symptoms of DPN.
L-arginine, the source of NO is released from proteins and small peptides in the small intestine and is then absorbed, along with other amino acids into the circulation from which it is delivered to every cell in the body. Some L-arginine is metabolized for NO synthesis and some is used for protein synthesis. In endothelial cells, the small cells that make up capillaries and line every blood vessel and lymph duct in the body, L-arginine can be converted to NO. The NO diffuses into the smooth muscle cells that surround the endothelial lining of blood vessels cells causing a biologic chain of events that lead to smooth muscle cell relaxation. This results in more blood flow to the tissues. Tissues that are hypoxic (deprived of good, normal circulation) can not produce as much NO as do normal, well-oxygenated tissues. Thus an initial period of hypoxia leads to declines in NO production and less and less blood flow over time, a vicious cycle to say the least. It is no wonder that diabetes is a progressive disease with wounds, kidney, heart, and eye disease becoming worse and worse over time. ”