Figure 50-14 Diagram describing the different mechanisms through which an initial increased production of oxidant free radicals might trigger a series of autocatalytic processes leading to further ^• O₂ ^- and peroxynitrite generation. Superoxide anion and peroxynitrite may result in uncoupling of nitric oxide synthase (NOS), sympathetic activation, inhibition of superoxide dismutase (SOD), and increased production and responsiveness to vasoconstrictors such as angiotensin II (AT II). These phenomena, in turn, might lead to further increases in oxidative stress. ET-1, endothelin-1; GTN, glyceryl trinitrate. (Redrawn from Gori T, Parker JD: Nitrate tolerance. A unifying hypothesis. Circulation 106:2510–2513, 2002.)