Journal
PEPTIDES
Volume 30, Issue 9, Pages 1729-1734Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2009.06.014
Keywords
Endothelium-dependent relaxation; GK rat; Mesenteric artery; NO; PAR2; Type 2 diabetes
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Open Research Center Project
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Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor that is proteolytically activated by certain endogenous proteases, such as trypsin, tryptase, and factor Xa. PAR2 can also be activated by synthetic peptides if their sequence mimics the tethered ligand exposed after receptor cleavage. Although it is known that PAR2 modulates vascular reactivity, it is unclear whether at the chronic stage of type 2 diabetes there are alterations in PAR2-mediated vascular responses. We investigated this issue by exposing mesenteric artery rings to PAR2-activating peptide (PAR2-AP; SLIGRL-NH2), the arteries used being obtained from later-stage (32-40-week-old) type 2 diabetic Goto-Kakizaki (GK) rats. The PAR2-AP-induced relaxation was enhanced in GK rats (vs. age-matched Wistar rats), whereas the ACh-induced relaxation was weaker in GK than in Wistar rats. In both groups, the PAR2-AP-induced relaxation was largely blocked by endothelial denudation or by N-G-nitro-L-arginine [nitric oxide (NO) synthase inhibitor] treatment, but it was unaffected by indomethacin (cyclooxygenase inhibitor) treatment. Both the NO production induced by PAR2-AP and the PAR2 protein expression were significantly increased in mesenteric arteries from GK rats (vs. Wistar rats). These data are the first to indicate that the PAR2-AP-induced endothelium-dependent relaxation is enhanced in mesenteric arteries isolated from type 2 diabetic GK rats at the chronic stage, and they further suggest that the enhancement may be due to an increased expression of PAR2 receptors in this artery. (C) 2009 Elsevier Inc. All rights reserved.
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