Receptor-activating peptides for PAR-1 and PAR-2 relax rat gastric artery via multiple mechanisms.
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.
Kawabata
Atsufumi
A
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
Nakaya
Yumiko
Y
Ishiki
Tsuyoshi
T
Kubo
Satoko
S
Kuroda
Ryotaro
R
Sekiguchi
Fumiko
F
Kawao
Naoyuki
N
Nishikawa
Hiroyuki
H
Kawai
Kenzo
K
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
D001685:Biological Factors; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D002118:Calcium