Nitric oxide (NO) synthase but not NO, HNO or H2O2 mediates endothelium-dependent relaxation of resistance arteries from patients with cardiovascular disease

M. Matthies, K. Rosenstand, I. Nissen, S. Muitjens, L.P. Riber, J.G.R. De Mey*, M. Bloksgaard

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background and Purpose Superoxide anions can reduce the bioavailability and actions of endothelium-derived NO. In human resistance-sized arteries, endothelium-dependent vasodilatation can be mediated by H2O2 instead of NO. Here, we tested the hypothesis that in resistance arteries from patients with cardiovascular disease, endothelium-dependent vasodilatation is mediated by a reactive oxygen species and not impaired by oxidative stress. Experimental Approach Small arteries were isolated from biopsies of the parietal pericardium of patients undergoing elective cardiothoracic surgery and were studied using immunohistochemical and organ chamber techniques. Key Results NO synthases 1, 2 and 3, superoxide dismutase 1 and catalase proteins were observed in the microvascular wall. Relaxing responses to bradykinin were endothelium dependent. During submaximal depolarization-induced contraction, bradykinin-mediated relaxations were inhibited by inhibitors of NO synthases (NOS) and soluble guanylyl cyclase (sGC) but not by scavengers of NO or HNO, inhibitors of cyclooxygenases, neuronal NO synthase, superoxide dismutase or catalase, or by exogenous catalase. During contraction stimulated by endothelin-1, these relaxations were not reduced by any of these interventions except DETCA, which caused a small reduction. Conclusion and Implications In resistance arteries from patients with cardiovascular disease, endothelium-dependent relaxations seem not to be mediated by NO, HNO or H2O2, although NOS and sGC can be involved. These vasodilator responses continue during excessive oxidative stress.
Original languageEnglish
Pages (from-to)1049-1064
Number of pages16
JournalBritish Journal of Pharmacology
Volume179
Issue number5
Early online date16 Nov 2021
DOIs
Publication statusPublished - Mar 2022

Keywords

  • bradykinin
  • coronary artery disease
  • endothelin-1
  • oxidative stress
  • superoxide dismutase
  • BRADYKININ-INDUCED RELAXATION
  • SOLUBLE GUANYLATE-CYCLASE
  • HYDROGEN-PEROXIDE
  • HYPERPOLARIZING FACTOR
  • CONCISE GUIDE
  • CENTER-DOT
  • NITROXYL
  • VASODILATION
  • PHARMACOLOGY
  • RESPONSES

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