Hydrogen sulfide (H2S) and nitric oxide (NO) are endogenously synthesized from L-cysteine and L-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H2S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1 beta (IL-1 beta). Although H2S by itself showed no effect on NO production, it augmented IL-beta-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-kappa B. IL-1 beta activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H2S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1 beta-induced NF-kappa B activation, iNOS expression, and NO production either in the absence or presence of H2S. Our findings suggest that H2S enhances NO production and iNOS expression by potentiating IL-10-induced NF-kappa B activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs. (c) 2006 Elsevier Inc. All rights reserved.