title: Remote arteriolar dilations caused by methacholine: a role for CGRP sensory nerves?
abstract: Remote vasodilation caused by arteriolar microapplication of acetylcholine cannot be completely attributed to passive cell-cell communication of a hyperpolarizing signal. The present study was undertaken to ascertain whether a neural component may be involved in the remote response. In the cheek pouch of anesthetized hamsters, methacholine (100 microM) was applied to the arteriole by micropipette for 5 s, and the arteriolar responses were measured at the site of application and at remote locations: 500 and 1,000 microm upstream from the application site. Superfusion with the local anesthetic bupivacaine attenuated a local dilatory response and abolished the conducted dilation response to methacholine. Localized micropipette application of bupivacaine 300 microm from the methacholine application site also attenuated the remote dilation but did not inhibit the local dilation. Blockade of neuromuscular transmission with botulinum neurotoxin A (1 U, 3 days), micropipette application of calcitonin gene-related peptide (CGRP) receptor inhibitor CGRP-(8-37) (10 microM) 300 microm upstream from the methacholine application site, and denervation of the CGRP sensory nerve by 2 days of capsaicin treatment reduced the conducted dilation response to methacholine but did not affect the local dilatory response. Together, these data support involvement of a TTX-insensitive nerve, specifically the CGRP containing nerve, in vascular communication. Understanding the effect of regulation of a novel neural network system on the vascular network may lead to a new insight into regulation of blood flow and intraorgan blood distribution.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Univ., 600 N. Wolfe St., Ross Rm. 351, Baltimore, MD 21287, USA.
authors.forename: Naris
authors.initials: N
authors.lastname: Thengchaisri
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rivers
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000294:innervation*; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D016210:Methacholine Chloride / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009465:Neuromuscular Agents / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000779:Anesthetics, Local; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D018721:Muscarinic Agonists; D009465:Neuromuscular Agents; D010446:Peptide Fragments; D016210:Methacholine Chloride; C058636:calcitonin gene-related peptide (8-37); D012964:Sodium; D019274:Botulinum Toxins, Type A; D015740:Calcitonin Gene-Related Peptide; D002045:Bupivacaine