Interaction of endogenous nitric oxide and calcitonin gene-related peptide
(cgrp) in sensory neuron-induced gastric vasodilation.
Chen, Richard Y. Z., and Paul H. Guth.
Anesthesiology, Medicine and Research Services, VAMC West Los Angeles and
UCLA School of Medicine, Los Angeles, CA
APStracts 2:0005G, 1995.
Stimulation of capsaicin sensitive sensory nerves (CPSN) induces gastric
mucosal hyperemia, which is mediated, in part, by both calcitonin gene
-related peptide (CGRP) and nitric oxide (NO). In the present study, we used
in vivo microscopy in anesthetized rats to 1) determine whether these agents
were being released locally at the submucosal level and, if so, 2) to test
the hypothesis that the CGRP dilates arterioles via release of endothelium
-derived NO (EDNO). Intragastric capsaicin (160 _M) dilated submucosal
arterioles from 25+/-3 to 67+/-8 _m. The intragastric capsaicin-induced
vasodilation was markedly reversed not only by intravenous administration of
the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), but
also by submucosal suffusion of either L-NAME or the CGRP receptor
antagonist, hCGRP8-37. The latter findings indicate that both NO and CGRP are
released locally at the submucosal level. Submucosal application of CGRP
induced dose-dependent dilation of gastric submucosal arterioles which was
significantly attenuated by L-NAME. Comparing at the same degree of
vasodilation (+42 _m), however, the dilation induced with submucosal CGRP was
much less attenuated by NO synthesis inhibition (-28%) than was that induced
with intragastric capsaicin (-79%). This indicates that EDNO released by CGRP
was not the only source of submucosal NO in the latter response. There must
be another, as yet undetermined, source of submucosal NO, e.g., possibly
nitroxidergic nerves.
Received 25 October 1993; accepted in final form 10 January 1995.
APS Manuscript Number G416-3.
Article publication pending Am. J. Physiol. (Gastrointest. Liver Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.