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 (50 mg/kg, i.p.) increased the Outer diameter of pial vessels by 50% in anesthetized animals at 30 film, and this effect was fully prevented by the administration of the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg, i.p. 15 min before GM1 injection). A 30 min exposure of cerebral cortex slices to GM1 (100 mu M) increased the content of nitrite plus nitrate (NOx) by 50%. Addition of L-NAME (100 mu M) to the incubation medium fully prevented GM1-induced NOx increase. Conversely, a 60 min exposure of slices to GM1 (100 mu M) decreased NOx content, revealing a biphasic effect of GM1. Our results suggest chat NO plays an important role in the vasodilation induced by GM1. (C) 2008 Elsevier Ltd. All rights reserved.