Pannexin 1 facilitates arterial relaxation via an endothelium-derived hyperpolarization mechanism

FEBS Lett. 2015 Apr 28;589(10):1164-70. doi: 10.1016/j.febslet.2015.03.018. Epub 2015 Mar 24.

Abstract

Pannexin 1 (Panx1) is involved in endothelium-dependent vasodilation in large arteries, but the exact mechanistic role remains poorly understood. We hypothesized that Panx1 facilitates large vessel relaxations regulating endothelium-derived hyperpolarization (EDH)-like mechanisms. The EDH-like component of acetylcholine-induced relaxation of saphenous arteries studied in isometric myograph after inhibition of NO-synthase and cyclooxygenase was significantly impaired in mice with genetically ablated Panx1 (KO) relative to that in the wild type (WT) mice. Application of P1-receptor antagonist and apyrase significantly reduced this component in WT, but not in KO mice, indicating participation of ATP released via Panx1 in the EDH-like relaxation.

Keywords: ATP; EDHF; Endothelium; Endothelium-derived hyperpolarization; Knockout mice; Pannexin 1; Pannexins; Saphenous artery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism
  • Animals
  • Apyrase / pharmacology
  • Arteries / metabolism
  • Connexins / genetics
  • Connexins / metabolism*
  • Endothelium, Vascular / metabolism*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Purinergic P1 Receptor Antagonists / pharmacology
  • Receptors, Purinergic P1 / genetics
  • Receptors, Purinergic P1 / metabolism
  • Vasodilation / drug effects
  • Vasodilation / physiology*

Substances

  • Connexins
  • Nerve Tissue Proteins
  • Panx1 protein, mouse
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Adenosine Triphosphate
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Apyrase