Modifications by sumatriptan and acetylcholine of nitric oxide-mediated neurogenic dilatation in dog cerebral arteries.
Canine cerebral arterial strips denuded of endothelium responded to nicotine and transmural electrical stimulation with relaxations, which were abolished by NG-nitro-L-arginine and methylene blue. Magnitudes of relaxation did not differ in the arteries contracted with prostaglandin F2alpha and sumatriptan, an effective therapeutic of migraine. Sumatriptan concentration-dependently contracted the arteries responding to 2 Hz stimulation with persistent relaxations, and the concentration of this 5-HT1B/1D/1F receptor agonist to overcome the relaxation averaged 1.06 x 10(-7) M. Acetylcholine inhibited the response to nerve stimulation due possibly to its action on prejunctional nitroxidergic nerves; the inhibition did not differ in the arteries contracted with prostaglandin F2alpha and K+. It appears that sumatriptan does not interfere with the release of nitric oxide from nerves but counteracts the neurogenic relaxation by functional antagonistic action on smooth muscle. Prejunctional inhibition by muscarinic receptor activation is unlikely associated with opening of neuronal K+ channels.
Ayajiki
K
K
Department of Pharmacology, Shiga University of Medical Science, Seta, 520-2192, Ohtsu, Japan.
Fujioka
H
H
Noda
K
K
Okamura
T
T
Toda
N
N
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D017366:Serotonin Receptor Agonists; D014665:Vasodilator Agents; D009569:Nitric Oxide; D009538:Nicotine; D018170:Sumatriptan; D015237:Dinoprost; D000109:Acetylcholine; D011188:Potassium