RÉSUMÉ
Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent vasodilators that have been shown to induce headache in migraine patients. Their antagonists are effective in the treatment of migraine attacks. In the present study, we hypothesize that vasodilation induced by the NO donor glyceryltrinitrate (GTN) or by CGRP is partially mediated via large conductance calcium-activated potassium (BK(Ca)) channels. The effects of the BK(Ca) channel selective inhibitor iberiotoxin on dural and pial vasodilation induced by CGRP, GTN and endogenously released CGRP by transcranial electrical stimulation (TES) were examined. Iberiotoxin significantly attenuated GTN-induced dural and pial artery dilation in vivo and in vitro, but had no effect on vasodilation induced by CGRP and TES. Our results show that GTN- but not CGRP-induced dural and pial vasodilation involves opening of BK(Ca) channels in rat.
Sujet(s)
Tête/vascularisation , Canaux potassiques calcium-dépendants de grande conductance/métabolisme , Neurostimulation électrique transcutanée , Vasodilatation/effets des médicaments et des substances chimiques , Vasodilatateurs/pharmacologie , Animaux , Peptide relié au gène de la calcitonine/pharmacologie , Artères cérébrales/effets des médicaments et des substances chimiques , Artères cérébrales/métabolisme , Dure-mère/vascularisation , Dure-mère/effets des médicaments et des substances chimiques , Dure-mère/métabolisme , Canaux potassiques calcium-dépendants de grande conductance/antagonistes et inhibiteurs , Fluxmétrie laser Doppler , Mâle , Artères méningées/effets des médicaments et des substances chimiques , Artères méningées/métabolisme , Monoxyde d'azote/métabolisme , Nitroglycérine/pharmacologie , Peptides/pharmacologie , Pie-mère/vascularisation , Pie-mère/effets des médicaments et des substances chimiques , Pie-mère/métabolisme , Rats , Rat Sprague-DawleyRÉSUMÉ
The aim of the present study was to examine the effect of K(ATP) channel openers pinacidil and levcromakalim on rat dural and pial arteries as well as their inhibition by glibenclamide. We used an in-vivo genuine closed cranial window model and an in-vitro organ bath. Glibenclamide alone reduced the dural but not the pial artery diameter compared with controls. Intravenous pinacidil and levcromakalim induced dural and pial artery dilation that was significantly attenuated by glibenclamide. In the organ bath pinacidil and levcromakalim induced dural and middle cerebral artery relaxation that was significantly attenuated by glibenclamide. In conclusion, K(ATP) channel openers induce increasing diameter/relaxation of dural and pial arteries after intravenous infusion in vivo and on isolated arteries in vitro. Furthermore, dural arteries were more sensitive to K(ATP) channel openers than pial arteries.