Does peroxynitrite stimulate cyclic GMP synthesis in rat aortic smooth muscle cells?
Peroxynitrite stimulates cyclic GMP synthesis in vascular smooth muscle and potentiates endothelial-dependent guanylate cyclase activation, suggesting it acts via low yields of nitric oxide or related derivatives.
Peroxynitrite stimulated the synthesis of cyclic GMP by rat aortic smooth muscle in a time- and dose-dependent manner. Peak formation of cyclic GMP occurred at 1 min with 100 microM peroxynitrite and was inhibited by oxyhemoglobin. Peroxynitrite was less potent than nitric oxide in stimulating cyclic GMP synthesis. Peroxynitrite also enhanced endothelial-dependent cyclic GMP synthesis, via generation of a long-lived substance, which was prevented by inhibition of glutathione synthesis. These data show that peroxynitrite stimulates cyclic GMP synthesis, inferring production of low yields of nitric oxide or associated derivatives. Additionally, vascular exposure to peroxynitrite potentiates endothelial-dependent activation of guanylate cyclase.
Tarpey et al. (Mon,) studied this question.