Endothelial dysfunction plays a major role in ischemic cardiovascular disease, hypertension and cerebrovascular disease. Endothelium (inner lining of blood vessels) produces chemicals which result in relaxation of blood vessel muscles so the blood vessels can dilate. Also, produced are chemicals which cause the blood vessels to constrict. An imbalance in this dilation and constriction can impair circulation to the tissues.
Nitrogen oxide (NO), mainly from arginine amino acid, is needed for dilation of blood vessels. Arginine is usually obtained from food. NO is constantly produced from available arginine with the enzyme NO synthase (NOS), producing NO and citrulline.
Another enzyme (arginase) converts arginine into ornithine and urea, reducing available arginine and causing blood vessel constriction. Forty percent of available arginine is destroyed by arginase. Arginase and NOS compete for available arginine. Usually, arginase activity is 1000 times that of NOS, and the resulting NO deficiency causes endothelial dysfunction and increased cardiovascular disease.
Inhibitors of arginase increase production of NO, relieving endothelial dysfunction, and allowing more circulation to reach the tissues. Pathology derives from increased arginase activity, and suppression of arginase reduces the risk of heart and blood vessel disease.
Endothelial dysfunction with over-constriction of blood vessels can be corrected by an inhibitor of the enzyme arginase, norvaline. This increases arginine levels and allows increased NO production. The authors demonstrated that norvaline suppression of arginase activity increases arginine reserves and increases production of NO.
CONCLUSION: Norvaline, an arginase inhibitor, reduces endothelial dysfunction in cases of NO deficiency by increasing the availability of arginine to produce NO.
NOTE: It is interesting that some authors note that our current tendency for arginine deficiency may be related to our current trend for cleanliness. Before people took so many showers and baths, their skin contained bacteria which converted ammonia from sweat into arginine. This could be absorbed easily into the body for increased production of NO.
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