Journal
JOURNAL OF VASCULAR RESEARCH
Volume 47, Issue 6, Pages 494-506Publisher
KARGER
DOI: 10.1159/000313877
Keywords
Endothelial cell; Proteinase-activated receptor; Rat aorta; Vasodilation; Oxidative stress; Trypsin
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [205920883]
- Yokoyama Rinsho Yakuri Foundation
- Takeda Science Foundation
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Background/Aims: The effects of oxidative stress on the vascular responsiveness to the agonists of proteinase-activated receptors (PARs) were investigated. Methods: Serum-free incubation was utilized to impose oxidative stress to isolated rat aortas. Spontaneously hypertensive rats (SHR) were investigated as a model of in vivo oxidative stress. Results: Thrombin, trypsin, PAR(1)-activating peptide (PAR(1)-AP), PAR(2)-AP and PAR(4)-AP induced little or no effect in the aortas of female Wistar-Kyoto rats (WKY). Serum-free incubation induced endothelium-dependent relaxant responses to PAR(2) agonists, but not PAR(1) or PAR(4) agonists, in a manner sensitive to diphenyleneiodonium or ascorbic acid. In male aortas, trypsin and PAR(2)-AP induced a transient endothelium-dependent relaxation without serum-free incubation. The acetylcholine-induced endothelium-dependent relaxation and the sodium nitroprusside-induced endothelium-independent relaxation remained unchanged. Immunoblot analyses revealed the upregulation of PAR(2) in endothelial cells, which was abolished by either diphenyleneiodonium or ascorbic acid. Aortas of female SHR expressed a higher level of PAR(2) than WKY and responded to trypsin without serum-free incubation. Treatment with ascorbic acid attenuated the trypsin-induced relaxation and the PAR(2) expression in SHR. Conclusion: This study provides the first evidence that oxidative stress upregulates PAR(2) in endothelial cells, thereby enhancing the endothelium-dependent relaxant response to PAR(2) agonists in rat aortas. Copyright (C) 2010 S. Karger AG, Basel
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