Sumatriptan inhibits neurogenic vasodilation of dural blood vessels in the anaesthetized rat--intravital microscope studies.
This study used intravital microscopy to measure the diameter of dural arteries in anaesthetized rats. Electrical stimulation of the surface of a closed cranial window produced increases in dural vessel diameter which were blocked by the CGRP receptor antagonist human-alpha CGRP(8-37) but unaffected by the NK1 receptor antagonist RP67580. Sumatriptan (3 and 10 mg kg-1, i.v.) significantly reduced the response to electrical stimulation. In contrast, sumatriptan (3 mg kg-1) had no effects on the response to exogenously administered CGRP. These results indicate that neurokinins play no role in neurogenic vasodilation in this preparation and that neurogenic vasodilation in rat dural vessels is mediated predominantly by CGRP. Furthermore, the data indicate that sumatriptan attenuates neurogenic vasodilation, probably by inhibiting the release of CGRP from perivascular trigeminal nerve endings innervating the dura. These experimental data parallel the clinical findings that CGRP levels are elevated in migraine and normalized, concomitantly with headache relief, by sumatriptan.
Williamson
D J
DJ
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Hargreaves
R J
RJ
Hill
R G
RG
Shepheard
S L
SL
D000344:Afferent Pathways / Q000187:drug effects; D000777:Anesthetics; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004388:Dura Mater / Q000098:blood supply*; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D018715:Microscopy, Video; D009412:Nerve Fibers / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology*; D014276:Trigeminal Nerve / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000777:Anesthetics; D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide