Production of Nitrosoglutathione Through Met Hemoglobin Reactions with Nitrite and Low Molecular Weight Thiols

Acellular hemoglobin (Hb) in the circulation, due to abnormal hemolysis is generally considered to be a source of toxicity. The toxicity is exacerbated by the presence of inflammatory conditions such as endothelial dysfunction that result in decreased levels of NO and nitrite in the plasma. Under some conditions, Hbs can actually generate bioactive NO that can compensate for depressed levels of NO due to inflammation and NO-dioxygenase activity of acellular Hbs. In the present work, we present a systematic biophysical study of how R and T state forms of met Hb in the presence of nitrite and thiols can generate nitrosoglutathione (GSNO). GSNO, an efficient vasodilator, is known to be in equilibrium with a pool of thiol/S-nitrosothiol containing proteins in blood vessels. Thus nitrite and thiol mediated GSNO production by acellular Hbs can be viewed as a means both to generate long lived forms of bioactive NO in the circulation and to replenish depleted S-nitrosothiol levels in the vasculature.