Sufentanil attenuates impairment of the endothelium-dependent vasodilation induced by hypoxia-reoxygenation in the rat coronary artery

Can J Physiol Pharmacol. 2016 Dec;94(12):1309-1314. doi: 10.1139/cjpp-2016-0037. Epub 2016 Jun 23.

Abstract

Sufentanil has been used broadly in cardiac surgery, but the mechanisms by which it modulates coronary vascular tone after ischemia-reperfusion injury are largely unknown. Effects of sufentanil on coronary tone and on the relaxation of rat coronary arteries (CAs) in response to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxing agents in the presence of hypoxia-reoxygenation (H/R) was studied in an in vitro organ chamber setup. Sufentanil (10-7-10-4 mol/L) relaxed rat CA rings in endothelium-dependent and endothelium-independent manners. In endothelium-intact rings, preincubation of H/R-treated CAs with sufentanil (10-5 mol/L) significantly increased the acetylcholine response, but did not augment sodium nitroprusside-induced relaxation. Sufentanil-mediated potentiation of acetylcholine-induced relaxation was not affected by a nitric oxide synthase inhibitor or by intermediate- or small-conductance Ca2+-activated K+ channel blockers. However, potentiation was abolished by iberiotoxin (100 nmol/L), a selective inhibitor of large-conductance Ca2+-activated K+ channels, as well as Rp-cAMPS (30 μmol/L), a cyclic AMP-dependent protein kinase (PKA) inhibitor. Sufentanil induced endothelium-dependent and endothelium-independent relaxation and attenuated H/R-induced impairment of endothelium-dependent vasodilation in the rat CAs. The potentiating effect of sufentanil may involve activation of large-conductance Ca2+-activated K+ channels via cAMP-dependent mechanisms.

Keywords: Ca2+-activated K+ channels; canaux K+ activés par le Ca2+; dépendant de l’endothélium; endothelium-dependent; hypoxia–reoxygenation; hypoxie–réoxygénation; relaxation; sufentanil.

MeSH terms

  • Animals
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Large-Conductance Calcium-Activated Potassium Channels / physiology
  • Male
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Sufentanil / pharmacology*
  • Vasodilation / drug effects*
  • Vasodilation / physiology

Substances

  • Large-Conductance Calcium-Activated Potassium Channels
  • Sufentanil