The relaxation induced by S-nitroso-glutathione and S-nitroso-N-acetylcysteine in rat aorta is not related to nitric oxide production

S-Nitroso-glutathione (GSNO) and S-nitroso-N-acetylcysteine (NACysNO) are n itrosothiols that release nitric oxide (NO) and mimic the effects of endoge nous NO. This study investigated the relaxation induced by GSNO and NACysNO in rat aorta and the relation between relaxation and NO formation. Both co mpounds at concentrations from 10(-9) M to 10(-4) M relaxed the rat aorta i n a concentration-dependent manner. However, NO production depended on the concentration of nitrosothiols present and was detected only above 100 muM GSNO or NACysNO. To determine whether K+ channels are involved in the relax ation induced by nitrosothiols, the contractions were induced with KCI at c oncentrations of 30, 60, or 90 mM. The concentration-effect curves for the relaxation induced by nitrosothiols were shifted to the right for all the K + concentrations compared with aortas precontracted with phenylephrine. The se results indicate the participation of K+ channels in the relaxation indu ced by GSNO and NACysNO. A selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, significantly inhibited the r elaxation induced by the nitrosothiols. The relaxation induced by GSNO and NACysNO was inhibited by the K+ channel blockers glibenclamide, selective K -ATP channels, and apamin, selective for low-conductance Ca2+-activated Kchannels in rat aorta, but was not inhibited by charybdotoxin, a potent and selective Ca2+-activated K+ channel blocker, or by 4-aminopyridine, a volt age-gated K+ channel blocker. These results indicate that relaxation induce d by GSNO and NACysNO is partially due to activation of K-ATP channels and partially due to activation of low-conductance Ca2+-activated K+ channels. However, the ability of the nitrosothiol compounds to overcome the inhibito ry effect of high extracellular K+ concentrations suggests another mechanis m of relaxation contributing to the nitrosothiol response. The most intrigu ing finding is that relaxation is not related to the NO produced in rat aor ta.