NO solution for a radical problem: a TAL story.

EVEN BEFORE the endothelium-derived relaxing factor (EDRF) was known to be nitric oxide (NO), it was recognized that it could be inactivated by the radical superoxide (O2 · ) (16). Once the EDRF was identified as NO, the chemistry underlying this phenomenon was obvious. Both NO and O2 · are radicals, and rapidly react with one another to form the strong oxidant peroxynitrite, which ultimately degrades to nitrite and nitrate (depending on other factors available in the reaction) (9). This simple chemical reaction between NO and O2 · has turned out to have enormous implications in biology and human pathophysiology. Oxidative inactivation of NO and formation of peroxynitrite play a role in endothelial dysfunction, ischemiareperfusion injury, neurodegenerative diseases, phagocytic killing of foreign organisms, cellular damage in sepsis, and many other states (2). In vessels, common conditions, such as hypercholesterolemia, diabetes, hypertension, cigarette smoking, and hypertension, promote a modest increase in O2 ·