title: The role of histamine in dural vessel dilation.
abstract: The pain of migraine is often throbbing suggesting an important role for the cranial blood vessels and their innervation by the trigeminal nerve. It is proposed that clinically effective anti-migraine compounds, such as 5-HT(1B/1D) agonists, have actions that include inhibiting calcitonin gene-related peptide (CGRP) release from trigeminal nerves. Human studies suggest that histamine can induce migraine possibly by activating nitric oxide (NO) synthase to promote endogenous NO production. The present studies investigated the effect of histamine and its antagonists on the cranial blood vessels using intravital microscopy to assess directly the diameter of dural arteries in sodium pentobarbitone anaesthetised rats. Electrical stimulation of a closed cranial window produces, by local depolarisation of nerves, dural vessel dilation that is monitored continuously on-line using video-microscopy and a video dimension analyser. Histamine infusion caused immediate and reproducible dilation of meningeal blood vessels (103.5+/-6%; n=40) that could be blocked by H(1)- (mepyramine) and H(2) (famotidine)-receptor antagonists (P<0.05), as well as a nitric oxide synthase inhibitor (N(G)-nitro-L-arginine methylester; P<0.05). Neurogenic dural vasodilation was not inhibited by H(2)-receptor antagonists, but was significantly inhibited by a H(1)-receptor antagonist at the high dose of 10 mg/kg. The present studies demonstrate that histamine is likely to activate NO synthase to promote NO production. There is also evidence that H(1)-receptors may be present on trigeminal neurones as the H(1)-receptor antagonist inhibited neurogenic vasodilation, albeit at a large dose.
authors.affiliation: Headache Group, Institute of Neurology, Queen Square, WC1N 3BG, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Akerman
authors.forename: David J
authors.initials: DJ
authors.lastname: Williamson
authors.forename: Holger
authors.initials: H
authors.lastname: Kaube
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D015738:Famotidine; D006632:Histamine; D019001:Nitric Oxide Synthase; D011738:Pyrilamine; D019331:NG-Nitroarginine Methyl Ester