Is circulating nitrite a directly acting vasodilator?

It can, therefore, be assumed that NO− # could act as an indirect vasodilator. In an article recently published in Clinical Science, Demoncheaux et al. [1] have addressed this issue by performing sophisticated experiments in vitro with rings of pulmonary arteries, and reported that the concentration of NO− # derived from dissolved NO (NO solv ) in aqueous solutions of NaNO # at pH 7.4 cannot account for the vasodilatory effects seen with NO− # (EC &! ̄ 4.5 μmol}l), compared with those of authentic NO (EC &! ̄ 0.84 nmol}l). Demoncheaux et al. [1] concluded that circulating NO− # (0.4 μmol}l and 13 μmol}l [2]) is a directly acting vasodilator, unlike other circulating carriers of NO, such as S-nitrosothiols (RSNOs), notably Snitrosoalbumin and S-nitrosohaemoglobin. In our opinion, this conclusion is incorrect. We think that the findings by Demoncheaux et al. [1] can be explained by the assumption that NO− # , i.e. HONO, acts indirectly as a vasodilator, i.e. by reacting with the sulphydryl group of thiols (RSHs) to form the very potent vasodilator RSNOs (eqn 3), the vasodilator activity of which may be severalfold higher (e.g. 80-fold higher for S-nitrosocysteine [3]) than that of authentic NO. HONO­RSH % H # O­RSNO (3)