CCK-evoked hyperemia in rat gastric mucosa involves neural mechanisms and nitric oxide.
This study was performed to identify the possible neural mechanisms and mediators that underlie the gastric mucosal hyperemia evoked by cholecystokinin octapeptide (CCK-8). Gastric mucosal blood flow in anesthetized rats was assessed by the clearance 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 iv infusion for 7 min) was abolished by inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (15 mg/kg iv) and significantly blunted by defunctionalization of afferent neurons with a neurotoxic dose 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 pharmacological maneuvers. The vasodilator response to low-dose CCK-8 (0.04 nmol/min) was further analyzed and found to be inhibited by acute bilateral subdiaphragmatic vagotomy, atropine (1 mumol/kg ip), and the antagonistic 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 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.
Heinemann
A
A
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Jocic
M
M
Peskar
B M
BM
Holzer
P
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation*; D006940:Hyperemia / Q000139:chemically induced*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009424:Nervous System Physiological Phenomena; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology*; D014628:Vagotomy
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide; D012844:Sincalide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester