Functional contribution of P2Y1 receptors to the control of coronary blood flow

Shawn B. Bender, Zachary C. Berwick, M. Harold Laughlin, Johnathan D. Tune

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Activation of ADPsensitive P2Y 1 receptors has been proposed as an integral step in the putative "nucleotide axis" regulating coronary blood flow. However, the specific mechanism(s) and overall contribution of P2Y 1 receptors to the control of coronary blood flow have not been clearly defined. Using vertically integrative studies in isolated coronary arterioles and open-chest anesthetized dogs, we examined the hypothesis that P2Y 1 receptors induce coronary vasodilation via an endothelium-dependent mechanism and contribute to coronary pressure-flow autoregulation and/or ischemic coronary vasodilation. Immunohistochemistry revealed P2Y 1 receptor expression in coronary arteriolar endothelial and vascular smooth muscle cells. The ADP analog 2-methylthio-ADP induced arteriolar dilation in vitro and in vivo that was abolished by the selective P2Y 1 antagonist MRS-2179 and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. MRS-2179 did not alter baseline coronary flow in vivo but significantly attenuated coronary vasodilation to ATP in vitro and in vivo and the nonhydrolyzable ATP analog ATPγS in vitro. Coronary blood flow responses to alterations in coronary perfusion pressure (40-100 mmHg) or to a brief 15-s coronary artery occlusion were unaffected by MRS-2179. Our data reveal that P2Y 1 receptors are functionally expressed in the coronary circulation and that activation produces coronary vasodilation via an endothelium/nitric oxide-dependent mechanism. Although these receptors represent a critical component of purinergic coronary vasodilation, our findings indicate that P2Y 1 receptor activation is not required for coronary pressure-flow autoregulation or reactive hyperemia.

Original languageEnglish (US)
Pages (from-to)1744-1750
Number of pages7
JournalJournal of Applied Physiology
Volume111
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • Ischemia
  • Isolated arteriole
  • Pressure-flow autoregulation
  • Reactive hyperemia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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