Hypoxic NO-donor nitrite protects sGC-dependently against morbidity and mortality associated with sterile inflammatory shock in mice

For a long time nitrite (NO2-) was believed to be an inert metabolite of the endogenous vasodilator NO. Recently, however, nitrite was identified as an important biologic NO reservoir in vasculature and tissues, contributing to hypoxic signaling, vasodilation and cytoprotection after ischemia-reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin or deoxymyoglobin, xanthine oxidase, mitochondria or NO synthase. Considering that NO may exert protective effects in inflammatory and septic shock, and that circulating nitrite may function as a source of NO in hypoxic and/or acidic conditions present in ischemic microvasculature of vital organs during shock, we decided to test the protective capacity of nitrite on toxicity associated with inflammatory shock.