Submitted on December 22, 2004
Accepted on March 8, 2005
Remote arteriolar dilations caused by methacholine: a role for CGRP sensory nerves
Richard J Rivers1* and Naris Thengchaisri1
1 Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA
* To whom correspondence should be addressed. E-mail: rrivers3{at}jhmi.edu.
Remote vasodilation caused by the arteriolar microapplication of acetylcholine can not be completely attributed to passive cell-cell communication of a hyperpolarizing signal. The present study was undertaken to ascertain whether there may be a neural component involved in the remote dilation. In the cheek pouch of anesthetized hamsters, methacholine (100 µM) was applied to the arteriole by micropipette for 5 seconds and the arteriolar responses were measured at the site of application and remote locations, 500 µm and 1000 µm upstream from the application site. Superfusion with local anesthetic bupivacaine attenuated local dilatory response and abolished conducted dilation to methacholine. Localized micropipette application of bupivacaine at 300 µm from the methacholine application site also attenuated the remote dilation, but without inhibition of the local dilatory response. Blockade of neuromuscular transmission using botulinum neurotoxin A (1 U, 3 days), application of calcitonin gene related peptide receptor inhibitor, CGRP8-37 (10 µM), micropipetted 300 µm upstream site from methacholine, and denervation of CGRP sensory nerve with 2 days of capsaicin treatment, all reduced the remote dilations to methacholine without affecting the local dilatory response. Together, these data support the involvement of TTX-insensitive nerve, specifically CGRP sensory nerve, in vascular communication. Understanding the regulation of novel neural network system on vascular network may lead to a new insight to the regulation of blood flow and intra-organ blood distribution.
