The cck-evoked hyperemia in the rat gastric mucosa involves neural
mechanisms and nitric oxide.
Heinemann, Akos, Milana Jocic, Brigitta M. Peskar, and Peter Holzer.
Department of Experimental and Clinical Pharmacology and Department
of Medicine, University of Graz, A-8010 Graz, Austria, and Department
of Experimental Clinical Medicine, University of Bochum, D-44780
Bochum, Germany
APStracts 2:0176G, 1995.
This study was performed to identify the possible neural mechanisms
and mediators which underlie the gastric mucosal hyperemia evoked by
cholecystokinin-octapeptide (CCK-8). Gastric mucosal blood flow in
anesthetized rats was assessed by the clearence of hydrogen and
gastric acid secretion determined in the luminally perfused stomach.
The gastric mucosal hyperemic effect of a low dose of CCK-8 (0.04
nmol min-1, infused iv for 7 min) was abolished by inhibition of
nitric oxide synthesis with NG-nitro-L-arginine methyl ester (15 mg
kg-1, iv) and significantly blunted by defunctionalization of
afferent neurons with a neurotoxic dose of capsaicin (125 mg kg-1,
sc). The hyperemic reaction to a high dose of CCK-8 (0.2 nmol min-1)
was not significantly affected by these pharmacological maneuvers.
The vasodilator response to low dose CCK-8 (0.04 nmol min-1) was
further analyzed and found to be inhibited by acute bilateral
subdiaphragmatic vagotomy, atropine (1 mol kg-1, ip) and the
antagonistic calcitonin gene-related peptide (CGRP) fragment CGRP8-37
(6 nmol min-1, ia). Cyclooxygenase inhibition with indomethacin (10
mg kg-1, ip) was ineffective. The CCK-8-induced increment of gastric
acid secretion was not significantly altered by any of these
procedures. These results indicate that the gastric vasodilator
effect of submaximal doses of CCK-8 is brought about by a vagovagal
reflex that involves acetylcholine, CGRP or a related peptide and
nitric oxide as vasodilator messengers.
Received 15 March 1995; accepted in final form 3 August 1995.
APS Manuscript Number G113-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.