CCK-EVOKED HYPEREMIA IN RAT GASTRIC-MUCOSA INVOLVES NEURAL MECHANISMSAND NITRIC-OXIDE

This study was performed to identify the possible neural mechanisms an d mediators that underlie the gastric mucosal hyperemia evoked by chol ecystokinin octapeptide (CCK-8). Gastric mucosal blood flow in anesthe tized rats was assessed by the clearance of hydrogen and gastric acid secretion determined in the luminally perfused stomach. The gastric mu cosal hyperemic effect of a low dose of CCK-8 (0.04 nmol/min iv infusi on for 7 min) was abolished by inhibition of nitric oxide synthesis wi th N-G-nitro-L-arginine methyl ester (15 mg/kg iv) and significantly b lunted by defunctionalization of afferent neurons with a neurotoxic do se of capsaicin (125 mg/kg sc). The hyperemic reaction to a high dose of CCK-8 (0.2 nmol/min) was not significantly affected by these pharma cological maneuvers. The vasodilator response to low-dose CCK-8 (0.04 nmol/min) was further analyzed and found to be inhibited by acute bila teral subdiaphragmatic vagotomy, atropine (1 mu mol/kg ip), and the an tagonistic calcitonin gene-related peptide (CGRP) fragment CGRP-(8-37) (6 nmol/ min ia). Cyclooxygenase inhibition with indomethacin (10 mg/ kg ip) was ineffective. The CCK-8-induced increment of gastric acid se cretion was not significantly altered by any of these procedures. Thes e results indicate that the gastric vasodilator effect of submaximal d oses of CCK-8 is brought about by a vagovagal reflex that involves ace tylcholine, CGRP or a related peptide, and nitric oxide as vasodilator messengers.