Conflict of Interest: None
Role of KATP Channels in Cephalic Vasodilatation Induced by Calcitonin Gene-Related Peptide, Nitric Oxide, and Transcranial Electrical Stimulation in the Rat
Version of Record online: 21 JUL 2008
Journal compilation © 2008 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 48, Issue 8, pages 1202–1213, September 2008
How to Cite
Gozalov, A., Jansen-Olesen, I., Klaerke, D. and Olesen, J. (2008), Role of KATP Channels in Cephalic Vasodilatation Induced by Calcitonin Gene-Related Peptide, Nitric Oxide, and Transcranial Electrical Stimulation in the Rat. Headache: The Journal of Head and Face Pain, 48: 1202–1213. doi: 10.1111/j.1526-4610.2008.01205.x
- Issue online: 2 SEP 2008
- Version of Record online: 21 JUL 2008
- Accepted for publication May 9, 2008.
- KATP channel;
- dural and pial artery;
- calcitonin gene-related peptide;
- transcranial electrical stimulation
Objective.— The objective of this study was to explore the role of KATP channels in vasodilatation induced by calcitonin gene-related peptide (CGRP), nitric oxide (NO), and transcranial electrical stimulation (TES) in intracranial arteries of rat.
Background.— Dilatation of cerebral and dural arteries causes a throbbing, migraine-like pain. Both CGRP and NO are potent vasodilators that can induce migraine. Their antagonists are effective in the treatment of migraine attacks. KATP channel openers cause headache in the majority of healthy subjects suggesting a role for KATP channels in migraine pathogenesis. We hypothesized that vasodilatation induced by CGRP and the NO donor glyceryltrinitrate (GTN) is mediated via KATP channels.
Methods.— We examined the effects of the KATP channel inhibitor glibenclamide on dural and pial vasodilatation induced by CGRP, NO, and endogenously released CGRP by TES. A rat genuine closed cranial window model was used for in vivo studies and myograph baths for studying the effect in vitro. In the closed cranial window model the diameter of dural vessels was measured directly in anesthetized animals to investigate the vascular effects of infused CGRP, NO, and endogenous CGRP after electrical stimulation. Also diameter changes of pial arteries, mean arterial blood pressure and local cerebral blood flow by Laser Doppler flowmetry (LCBFFlux) were measured.
Results.— CGRP, NO, and TES caused dilatation of the 2 arteries in vivo and in vitro. In anesthetized rats glibenclamide significantly attenuated CGRP induced dural and TES induced dural/pial artery dilatation (P = .001; P = .001; P = .005), but had no effect on dural/pial vasodilatation induced by GTN. In vitro glibenclamide failed to significantly inhibit CGRP- and GTN-induced vasodilatation.
Conclusions.— These results show that a KATP channel blocker in vivo but not in vitro inhibits CGRP, but not GTN-induced dilatation of dural and pial arteries, a mechanism thought to be important in migraine.