Distinct roles for protease-activated receptors 1 and 2 in vasomotor modulation in rat superior mesenteric artery.
OBJECTIVE
Protease-activated receptors (PARs) 1 and 2 are expressed in various blood vessels including rat aorta, modulating vascular tone. We investigated the roles of PAR-1 and PAR-2 in vasomotor modulation in rat superior mesenteric artery.


RESULTS
Effects of the PAR-2-activating peptide Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-amide) and the PAR-1-activating peptide Thr-Phe-Leu-Leu-Arg-amide (TFLLR-amide) on isometric tension were examined in isolated rat superior mesenteric artery or aorta. Both SLIGRL-amide and TFLLR-amide caused relaxation in the precontracted rat aortic rings. The latter peptide, but not the former, produced contraction in the resting rings. NG-nitro-L-arginine methyl ester (L-NAME), but not apamin/charybdotoxin known to block the endothelium-derived hyperpolarizing factor (EDHF) pathway, abolished the relaxation and facilitated the contraction. In the precontracted rat superior mesenteric artery, SLIGRL-amide, but not TFLLR-amide, elicited endothelium-dependent relaxation, which was only partially inhibited by L-NAME with and without indomethacin. The residual relaxation was abolished by apamin/charybdotoxin. Carbenoxolone, a gap junction inhibitor, significantly attenuated the SLIGRL-amide-evoked, EDHF-dependent relaxation, although neither 17-octadecynoic acid, a P450 epoxygenase inhibitor, nor catalase, a hydrogen peroxide scavenger, revealed inhibitory effects. The residual response resistant to carbenoxolone was unaffected by ouabain/BaCl2. In the resting artery, TFLLR-amide, but not SLIGRL-amide, produced only slight contraction, which was dramatically facilitated by combination of L-NAME and apamin/charybdotoxin or by removal of the endothelium.


CONCLUSIONS
Our data suggest that, in rat superior mesenteric artery, endothelial PAR-2, upon activation, causes relaxation via both NO and EDHF pathways, and that activation of muscular PAR-1 exhibits potential contractile activity that is largely masked by NO and EDHFs pathways triggered by endothelial PAR-1. Gap junctions might be involved in the EDHF mechanisms in this artery.
Division of Physiology and Pathophysiology, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowake, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
Atsufumi
A
Kawabata
Satoko
S
Kubo
Yumiko
Y
Nakaya
Tsuyoshi
T
Ishiki
Ryotaro
R
Kuroda
Fumiko
F
Sekiguchi
Naoyuki
N
Kawao
Hiroyuki
H
Nishikawa
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000502:physiology*; D044464:Receptor, PAR-2 / Q000502:physiology*; D014357:Trypsin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D009842:Oligopeptides; C462999:PAR-1-activating peptide; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D019001:Nitric Oxide Synthase; D014357:Trypsin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin