Nitric oxide and potassium channels mediate GM1 ganglioside-induced vasorelaxation.

Monosialotetrahexosylganglioside (GM1) is a glycosphingolipid present in most cell membranes that displays antioxidant and neuroprotective properties. It has been recently described that GM1 induces pial vessel vasodilation and increases NO( x ) content in cerebral cortex, which are fully prevented by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). However, it is not known whether GM1 relaxes larger vessels, as well as the mechanisms by which GM1 causes vasorelaxation. In this study, we demonstrate that GM1 (10, 30, 100, 300 microM, 1 and 3 mM) induces vascular relaxation determined by isometric tension studies in rat mesenteric artery rings contracted with 1 microM phenylephrine. The vasorelaxation induced by GM1 was abolished by endothelium removal, by incubation with L-NAME (1 microM), and partially inhibited by the blockade of potassium channels by 1 mM tetraethylammonium, 10 microM glibenclamide, by the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (10 microM), and by 50 nM charybdotoxin, a blocker of large and intermediate conductance calcium-activated potassium channels. Moreover, GM1-induced relaxation was not affected by apamin (50 nM), a small conductance calcium-activated potassium channel blocker. The results indicate that direct and indirect nitric oxide pathways play a pivotal role in vasorelaxation induced by GM1, which is mediated mainly by potassium channels activation. We suggest that vasodilation may underlie some of the biological effects of exogenous GM1 ganglioside.