Influence of sulfites on the action of nitric oxide and s-nitrosoglutathione in vitro and in vivo

Sulfur IV compounds (sulfur dioxide, bisulfite and sulfite) have been shown to react rapidly with nitric oxide and with S-nitrosothiol carriers of nitric oxide (Harvey/Nelsestuen, (1995) Biochim. Biophys. Actal26L 41-44). In this study we examine the interaction between sulfites, nitric oxide and S-nitrosothiol compounds. Mass spectroscopy and tests for free sulfhydryls suggest that the reaction between sulfites and S-nitrosoglutathione (GSNO) produces a sulfonated product (RSSO₃-) with release of NO-. Contracted blood vessels were induced to relax by exposure to exogenous nitric oxide (or GSNO). This relaxation was inhibited by micromolar concentrations of sulfites. Relaxation due to acetylcholine-induced endogenous nitric oxide production by endothelial cells was not effected by sulfites. Thus it appeared that sulfites did not interfere with tightly coupled cell-cell signaling by nitric oxide. Intravenous injection of GSNO in anesthetized rats results in rapid, transient decrease in mean arterial blood pressure. Intravenous addition of sulfites prior to the injection of the GSNO abolished this effect, further demonstrating the ability of sulfites to interfere with the proper functioning of nitric oxide carriers. These results show that sulfur IV exposure has the potential to deplete extracellular pools of S-nitrosothiol compounds such as those found in the fluids lining the lungs. If these pools are important for maintenance of smooth muscle tone, the sulfite-nitric oxide reaction may be an important mechanism underlying the adverse respiratory effects of sulfites.