Protease activated receptors modulate aortic vascular tone

Harold I. Magazine, Jonathan M. King, Kamal D. Srivastava

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The effect of agonists of the known protease activated receptors (PAR), the thrombin and the PAR-2 receptors, on vasoactive mediator release and vascular tone were studied using rings of rat aorta. Stimulation of aortic rings with the thrombin receptor agonist, Trap-14, or the PAR-2 agonist, SLIGRL, resulted in a rapid release of nitric oxide. Trap-14 and SLIGRL-induced nitric oxide release was reduced by pre-treatment with BQ-788, an ET(B) endothelin receptor-specific antagonist. Consistent with a role for endothelin-1 receptor activation in Trap-14 and SLIGRL-induced nitric oxide release, endothelin-1 levels were increased significantly following 5 min treatment of aortic rings with Trap-14 or SLIGRL. Cumulative addition of Trap-14 to aortic rings denuded of endothelium resulted in dose-dependent contraction with an EC50 value of 23 ± 5 μM, whereas SLIGRL addition failed to induce aortic contraction. These data suggest that the known protease activated receptors are functionally coupled to nitric oxide release. In addition, the thrombin receptor appears to modulate both vasodilator and contractile responses, whereas the PAR-2 receptor is linked only to vasodilation.

Original languageEnglish (US)
Pages (from-to)S75-S80
JournalInternational Journal of Cardiology
Volume53
Issue numberSUPPL.
DOIs
StatePublished - Apr 26 1996
Externally publishedYes

Keywords

  • Endothelin
  • Nitric oxide
  • Protease activated receptors
  • Thrombin receptors
  • Vascular tone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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