Role of BK(Ca) channels in cephalic vasodilation induced by CGRP, NO and transcranial electrical stimulation in the rat.
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.
Gozalov
A
A
Danish Headache Centre and Department of Neurology, and Department of Clinical Experimental Research, Glostrup Hospital, University of Copenhagen, DK-2600 Glostrup, Denmark. dragozalov@yahoo.com
Jansen-Olesen
I
I
Klaerke
D
D
Olesen
J
J
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D006257:Head / Q000098:blood supply*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D004561:Transcutaneous Electric Nerve Stimulation; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D014665:Vasodilator Agents; D009569:Nitric Oxide; C064719:iberiotoxin; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide