Binding of nitric oxide to thiols and hemes in hemoglobin H: implications for alpha-thalassemia and hypertension.

Our earlier studies suggested an association between alpha-thalassemia and hypertension. We postulated that this association might involve trapping of the vasodilator nitric oxide (NO) by hemoglobin (Hb). Hb A has recently been shown to carry NO on its sulfhydryl groups in addition to its hemes. In this report we studied the interaction of purified Hb H as well as Hb A with NO. The number of reactive sulfhydryls were determined spectrophotometrically with bis-dithionitrobenzoate. Spectral studies and nitrosothiol measurements after treatment with NO or nitrosothiols indicated that all eight reactive sulfhydryls of Hb H were capable of binding NO. Hb A, however, was only able to bind and transfer two molecules of NO per tetramer. These findings support the biochemical basis for the association between alpha-thalassemia and hypertension.