Nitroglycerin-induced nNOS increase in rat trigeminal nucleus caudalis is inhibited by systemic administration of lysine acetylsalicylate but not of sumatriptan.
Systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor, in migraineurs triggers after several hours an attack of which the precise mechanisms are unknown. We found previously in rats that nitroglycerin (10 mg/kg s.c.) is able to increase significantly after 4 h the number of neuronal nitric oxide synthase (nNOS)-immunoreactive neurones in the cervical part of trigeminal nucleus caudalis. In the present experiments, we demonstrate that the 5-HT1B/D agonist sumatriptan (0.6 mg/kg s.c.) does not alter this phenomenon when given before NTG. By contrast, pretreatment with lysine acetylsalicylate (50 mg/kg i.m.) attenuates the NTG-induced nNOS expression in the superficial laminae of trigeminal nucleus caudalis. These findings suggest that effect of NTG on nNOS at a high dosage may involve the cycloxygenase pathway and that activation of the peripheral 5-HT1B/D receptors is not able to modify this effect. These data could help to better understand the role of NO in the pathogenesis of headaches and the action of antimigraine drugs.
Pardutz
A
A
Research Centre of Cellular & Molecular Neurobiology, Headache Research Unit, Universtiy og Liège, Liè, Belgium.
Szatmári
E
E
Vecsei
L
L
Schoenen
J
J
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018170:Sumatriptan / Q000494:pharmacology*; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects* / Q000201:enzymology*
D018170:Sumatriptan; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D005996:Nitroglycerin; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate