Intravital microscope studies on the effects of neurokinin agonists and calcitonin gene-related peptide on dural vessel diameter in the anaesthetized rat

Authors

  • DJ Williamson,

    1. Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK
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  • RJ Hargreaves,

    1. Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK
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  • RG Hill,

    1. Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK
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  • SL Shepheard

    Corresponding author
    1. Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK
      Sl. Shepheard, Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Ccntre, Terlings Park, Harlow Essex, UK. Tel. +44 (0)1279 440000, fax. +44 (0)1279 440390, e-mail: sara_shepheard@merck.com..
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Sl. Shepheard, Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Ccntre, Terlings Park, Harlow Essex, UK. Tel. +44 (0)1279 440000, fax. +44 (0)1279 440390, e-mail: sara_shepheard@merck.com..

Abstract

This study describes a novel intravital microscope technique for direct measurement of dural blood vessel diameter through a closed cranial window in anaesthetized rats. This technique avoids removal of the skull which can lead to problems o altered vessel reactivity and brain swelling that are encountered with open cranial window techniques. Substance P and calcitonin gene-related (CGRP) evoked increases in dura vessel diameter, which were abolished by the NK1 receptor antagonist, RP67580 and the CGRP receptor antagonist, human-CGRP(8–31) respectively. Neurokinin A produced increases in dural vessel diameter which were unaffected by the NK2 receptor antagonist SR 48968 but were blocked by RP67580, suggesting that neurokinin A can act through NK1 receptors to produce dural vasodilation in rats. The NK3 receptor agonist, senktide, had no effects on dural vessel diameter. All drugs were administered intravenously. In humans, vasodilation within the meningeal vasculature has been implicated in the pathogenesis of migraine, the present experiments indicate that substance P or neurokinin A (both acting through NK1 receptors) or CGRP may be responsible.

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