Modifications by sumatriptan and acetylcholine of nitric oxide-mediated neurogenic dilatation in dog cerebral arteries

Canine cerebral arterial strips denuded of endothelium responded to nicotin e and transmural electrical stimulation with relaxations, which were abolis hed by NG-nitro-L-arginine and methylene blue. Magnitudes of relaxation did not differ in the arteries contracted with prostaglandin F2 alpha and suma triptan, an effective therapeutic of migraine. Sumatriptan concentration-de pendently contracted the arteries responding to 2 Hz stimulation with persi stent 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 p rejunctional nitroxidergic nerves; the inhibition did not differ in the art eries contracted with prostaglandin F-2 alpha and K+. It appears that sumat riptan 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 i s unlikely associated with opening of neuronal K+ channels. (C) 2001 Elsevi er Science B.V. All rights reserved.