title: Receptor-activating peptides for PAR-1 and PAR-2 relax rat gastric artery via multiple mechanisms.
abstract: Receptor-activating peptides for protease-activated receptors (PARs) 1 or 2 enhance gastric mucosal blood flow (GMBF) and protect against gastric mucosal injury in rats. We thus examined and characterized the effects of PAR-1 and PAR-2 agonists on the isometric tension in isolated rat gastric artery. The agonists for PAR-2 or PAR-1 produced vasodilation in the endothelium-intact arterial rings, which was abolished by removal of the endothelium. The mechanisms underlying the PAR-2- and PAR-1-mediated relaxation involved NO, endothelium-derived hyperpolarizing factor (EDHF) and prostanoids, to distinct extent, as evaluated by use of inhibitors of NO synthase, cyclo-oxygenase and Ca2+-activated K+ channels. The EDHF-dependent relaxation responses were significantly attenuated by gap junction inhibitors. These findings demonstrate that endothelial PAR-1 and PAR-2, upon activation, dilate the gastric artery via NO and prostanoid formation and also EDHF mechanisms including gap junctions, which would enhance GMBF.
authors.affiliation: Division of Physiology and Pathophysiology, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishiki
authors.forename: Satoko
authors.initials: S
authors.lastname: Kubo
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Kuroda
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kawai
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology; D001685:Biological Factors / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D005753:Gastric Mucosa / Q000098:blood supply*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000502:physiology*; D044464:Receptor, PAR-2 / Q000502:physiology*; D014664:Vasodilation
chemical_list: D001685:Biological Factors; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D002118:Calcium