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.
Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil. furian.anaflavia@gmail.com
Ana Flávia
AF
Furian
Mauro Schneider
MS
Oliveira
Danieli Valnes
DV
Magni
Mauren Assis
MA
Souza
Vanessa Trindade
VT
Bortoluzzi
Lívia Maronesi
LM
Bueno
Luiz Fernando Freire
LF
Royes
Carlos Fernando
CF
Mello
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000098:blood supply*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D005677:G(M1) Ganglioside; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester