INTRAVITAL MICROSCOPE STUDIES ON THE EFFECTS OF NEUROKININ AGONISTS AND CALCITONIN-GENE-RELATED PEPTIDE ON DURAL VESSEL DIAMETER IN THE ANESTHETIZED RAT

This study describes a novel intravital microscope technique for direc t measurement of dural blood vessel diameter through a closed cranial window in anaesthetized rats. This technique avoids removal of the sku ll, which can lead to problems of altered vessel reactivity and brain swelling that are encountered with open cranial window techniques. Sub stance P and calcitonin gene-related (CGRP) evoked increases in dural vessel diameter, which were abolished by the NK1 receptor antagonist, RP67580 and the CGRP receptor antagonist, human-alpha CGRP((8-37)) res pectively Neurokinin A produced increases in dural vessel diameter whi ch were unaffected by the NK2 receptor antagonist SR 48968 but were bl ocked by RP67580 suggesting that neurokinin A can act through NK1 rece ptors to produce dural vasodilation in rats. The NK3 receptor agonist, senktide, had no effects on dural vessel diameter. All drugs were adm inistered intravenously. In humans, vasodilation within the meningeal vasculature has been implicated in the pathogenesis of migraine, the p resent experiments indicate that substance P or neurokinin A (both act ing through NK1 receptors) or CGRP may be responsible.