Remote arteriolar dilations caused by methacholine: a role for CGRP sensory nerves?

Abstract

Thengchaisri, Naris, and Richard J. Rivers. Remote arteriolar dilations caused by methacholine: a role for CGRP sensory nerves? Am J Physiol Heart Circ Physiol 289: H608 -H613, 2005. First published March 11, 2005 doi:10.1152/ajpheart.01290.2004.-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 M) 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 m 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 m 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 M) 300 m 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.

Properties of submucosal venules in the rat distal colon

“…This dilatory response was sensitive to TTX, but was not completely abolished by TTX. This is consistent with previous reports showing that TTX-resistant CGRPcontaining primary afferent nerves are involved in vasodilation (Thengchaisri and Rivers, 2005), and that action potential conduction of capsaicin-sensitive primary afferents innervating the submucosal arteriole of the intestines was reported to be TTX-resistant (Miranda-Morales et al, 2010). TTX-resistant voltage-gated Na + current has been reported in capsaicin-sensitive primary afferents innervating the rat distal colon (Su et al, 1999).…”

Oxygen-Dependent Vasomotor Responses Are Conducted Upstream in the Mouse Cremaster Microcirculation

“…However, this seems to be a less likely possibility. Although there is experimental evidence that perivascular nerves can contribute to conducted vasomotor responses [33], there is an overwhelming body of evidence showing that the major mechanism for conducted vasomotor responses is gap junction-mediated cell-cell communication between the endothelial and/or vascular smooth muscle cells of the vessel wall [6,7]. …”

The Vascular Conducted Response in Cerebral Blood Flow Regulation

“…Previous studies suggested that voltage-gated Na þ channels may be expressed in the vascular wall, either in ECs 53 or in sensory nerve terminals adjacent to arteriolar VSMCs 55 and that activation of these channels might contribute to the regenerative conduction process. This topic is still not completely resolved, but recent studies did not find a role for TTX-sensitive 13,25,29 or TTX-insensitive Na þ channels 18 in conducted depolarization in rat renal or mesenteric arterioles.…”