Upregulation of proteinase-activated receptor-2 and increased response to trypsin in endothelial cells after exposure to oxidative stress in rat aortas

Murasaki Aman, Mayumi Hirano, Hideo Kanaide, Katsuya Hirano

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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, PAR1-activating peptide (PAR1-AP), PAR2-AP and PAR4-AP induced little or no effect in the aortas of female Wistar-Kyoto rats (WKY). Serum-free incubation induced endothelium-dependent relaxant responses to PAR2 agonists, but not PAR1 or PAR4 agonists, in a manner sensitive to diphenyleneiodonium or ascorbic acid. In male aortas, trypsin and PAR2-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 PAR2 in endothelial cells, which was abolished by either diphenyleneiodonium or ascorbic acid. Aortas of female SHR expressed a higher level of PAR2 than WKY and responded to trypsin without serum-free incubation. Treatment with ascorbic acid attenuated the trypsin-induced relaxation and the PAR2 expression in SHR. Conclusion: This study provides the first evidence that oxidative stress upregulates PAR2 in endothelial cells, thereby enhancing the endothelium-dependent relaxant response to PAR2 agonists in rat aortas.

Original languageEnglish
Pages (from-to)494-506
Number of pages13
JournalJournal of Vascular Research
Volume47
Issue number6
DOIs
Publication statusPublished - Oct 2010

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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