title: CCK-evoked hyperemia in rat gastric mucosa involves neural mechanisms and nitric oxide.
abstract: 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.
authors.affiliation: Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Heinemann
authors.forename: M
authors.initials: M
authors.lastname: Jocic
authors.forename: B M
authors.initials: BM
authors.lastname: Peskar
authors.forename: P
authors.initials: P
authors.lastname: Holzer
mesh_terms: 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
chemical_list: 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