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.
Furian
Ana Flávia
AF
Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.
Rattmann
Yanna Dantas
YD
Oliveira
Mauro Schneider
MS
Royes
Luiz Fernando Freire
LF
Marques
Maria Consuelo Andrade
MC
Santos
Adair Roberto Soares
AR
Mello
Carlos Fernando
CF
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D015221:Potassium Channels; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005677:G(M1) Ganglioside; D006162:Guanylate Cyclase