Pericardial fluid of cardiac patients elicits arterial constriction: role of endothelin-1

Can J Physiol Pharmacol. 2015 Sep;93(9):779-85. doi: 10.1139/cjpp-2015-0030. Epub 2015 Apr 17.

Abstract

Recently, several vasoactive molecules have been found in pericardial fluid (PF). Thus, we hypothesized that in coronary artery disease due to ischemia or ischemia-reperfusion, the level of vasoconstrictors, mainly endothelin-1 (ET-1), increases in PF, which can increase the vasomotor tone of arteries. Experiments were performed using an isometric myograph. Vasomotor effects of PF from patients undergoing coronary artery bypass graft (PFCABG, n = 14) or valve replacement (PFVR, n = 7) surgery were examined in isolated rat carotid arteries (N = 14; n = 26). Vasomotor responses to KCl (40 or 60 mmol/L) were also tested. The selective endothelin A receptor antagonist BQ123 (10(-6) mol/L) was used to elucidate the role of ET-1. Both the first and the second additions of KCl elicited increases in the isometric force of the isolated arteries (KCl1, 6.1 ± 0.2 mN; KCl2, 6.5 ± 0.9 mN). PFCABG and PFVR elicited substantial increases in the isometric force of arteries (PFCABG, 3.1 ± 0.7 mN; PFVR, 3.0 ± 0.9 mN; p > 0.05). The presence of the selective endothelin A receptor blocker significantly reduced arterial contractions to PFCABG (before BQ123, 2.6 ± 0.5 mN vs. after BQ123, 0.8 ± 0.1 mN; p < 0.05). This study is the first to demonstrate that PFs of patients elicit substantial arterial constrictions, which is mediated primarily by ET-1. Interfering with the vasoconstrictor action of PF could be a potential therapeutic target to improve coronary blood flow in cardiac patients.

Keywords: ET-1 receptor; contraction isométrique; coronary bypass; isometric contraction; liquide péricardique; pericardial fluid; pontage coronarien; remplacement valvulaire; récepteur de l’ET-1; valve replacement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Arteries / physiology*
  • Coronary Artery Disease* / surgery
  • Endothelin Receptor Antagonists / pharmacology
  • Endothelin-1 / analysis
  • Endothelin-1 / physiology*
  • Humans
  • In Vitro Techniques
  • Male
  • Peptides, Cyclic / pharmacology
  • Pericardial Fluid / chemistry*
  • Pericardial Fluid / physiology*
  • Potassium Chloride / pharmacology
  • Rats
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Peptides, Cyclic
  • Potassium Chloride
  • cyclo(Trp-Asp-Pro-Val-Leu)