L-NAME prevents GM1 ganglioside-induced vasodilation in the rat brain

Monosialoganglioside (GM1) is a glycosphingolipid present in most cell membranes that displays antioxidant and neuroprotective properties. It has been recently described that GM1 induces vasodilation. However, the mechanisms underlying GM1-induced vasodilation were not evaluated to date. Therefore, in this study we investigated whether the nonspecific NOS inhibitor l-NAME prevents GM1-induced vasodilation in rats. The systemic injection of GM1 (50mg/kg, i.p.) increased the outer diameter of pial vessels by 50% in anesthetized animals at 30min, and this effect was fully prevented by the administration of the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 60mg/kg, i.p. 15min before GM1 injection). A 30min exposure of cerebral cortex slices to GM1 (100microM) increased the content of nitrite plus nitrate (NOx) by 50%. Addition of l-NAME (100microM) to the incubation medium fully prevented GM1-induced NOx increase. Conversely, a 60min exposure of slices to GM1 (100microM) decreased NOx content, revealing a biphasic effect of GM1. Our results suggest that NO plays an important role in the vasodilation induced by GM1.