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 journalArticleAcademicpeer-review

4 Citations (Web of Science)

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 H2O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H2O2 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 H2O2 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 H2O2 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 H2O2. Furthermore, the candidate endothelium-derived relaxing factor H2O2 also acts as an endothelium-dependent vasodilator.
Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalBasic & Clinical Pharmacology & Toxicology
Volume122
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • CARDIOVASCULAR-DISEASE
  • HYPERPOLARIZING FACTOR
  • THERAPEUTIC TARGET
  • CONCISE GUIDE
  • DYSFUNCTION
  • ACTIVATION
  • MECHANISMS
  • SYSTEM
  • VASOCONSTRICTION
  • RELAXATIONS

Cite this