Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

Thomas M Leurgans, Maria Bloksgaard, Akhmadjon Irmukhamedov, Lars P. Riber, Jo G R De Mey*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K + or the TxA 2 analogue U46619 and by H 2O 2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H 2O 2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K +, the TXA 2 analogue U46619 or ET-1. Effects of the NO donor Na-nitroprusside (SNP) and of exogenous H 2O 2 were recorded in the absence and presence of inhibitors of cyclooxygenases, NO synthases and small and intermediate conductance calcium-activated K + channels. During contractions induced by either of the three stimuli, the potency of SNP did not differ and was not modified by the inhibitors. In vessels contracted with ET-1, the potency of H 2O 2 was on average and in terms of interindividual variability considerably larger than in K +-contracted vessels. Both differences were not statistically significant in the presence of inhibitors of mechanisms of endothelium-dependent vasodilatation. In resistance arteries from patients with cardiovascular disease, ET-1 does not selectively modify smooth muscle relaxing responses to NO or H 2O 2. Furthermore, the candidate endothelium-derived relaxing factor H 2O 2 also acts as an endothelium-dependent vasodilator.

Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Volume122
Issue number1
Pages (from-to)74–81
ISSN1742-7835
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Aged
  • Cardiovascular Diseases/physiopathology
  • Coronary Vessels/drug effects
  • Endothelin-1/metabolism
  • Endothelium, Vascular/drug effects
  • Female
  • Humans
  • Hydrogen Peroxide/pharmacology
  • Male
  • Muscle, Smooth, Vascular/drug effects
  • Nitric Oxide/pharmacology
  • Nitroprusside/pharmacology
  • Pericardium/physiopathology
  • Vasodilation/drug effects
  • Vasodilator Agents/pharmacology

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