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NO Synthase but not NO, HNO or H2O2 Mediates Endothelium-Dependent Relaxation of Resistance Arteries from Patients with Resistant Cardiovascular Disease
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  • Maximilian Matthies,
  • Kristoffer Rosenstand,
  • Inger Nissen,
  • Stan Muitjens,
  • Lars Riber,
  • Jo De Mey,
  • Maria Bloksgaard
Maximilian Matthies
University of Southern Denmark

Corresponding Author:mmatthies@health.sdu.dk

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Kristoffer Rosenstand
University of Southern Denmark
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Inger Nissen
Institute of Molecular Medicine, University of Southern Denmark
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Stan Muitjens
University of Southern Denmark
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Lars Riber
Odense University Hospital
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Jo De Mey
Syddansk Universitet Det Sundhedsvidenskabelige Fakultet
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Maria Bloksgaard
Molecular Medicine
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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. We tested the hypotheses that in resistance arteries from patients with resistant cardiovascular disease (CVD), endothelium-dependent vasodilatation uses mechanisms that are either insensitive to oxidative stress or involve a reactive oxygen species. Experimental Approach: Small arteries were isolated from biopsies of the parietal pericardium of patients undergoing elective cardiothoracic surgery and were studied by 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, these 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 resistant CVD, endothelium-dependent relaxations seem not to be mediated by NO, HNO or H2O2 although NOS and sGC can be involved. These vasodilator responses proceed during excessive oxidative stress.
11 Feb 2021Submitted to British Journal of Pharmacology
12 Feb 2021Submission Checks Completed
12 Feb 2021Assigned to Editor
21 Feb 2021Reviewer(s) Assigned
15 Mar 2021Review(s) Completed, Editorial Evaluation Pending
30 Mar 2021Editorial Decision: Revise Minor
07 Jun 20211st Revision Received
18 Jun 2021Submission Checks Completed
18 Jun 2021Assigned to Editor
27 Jun 2021Reviewer(s) Assigned
30 Aug 2021Review(s) Completed, Editorial Evaluation Pending
07 Sep 2021Editorial Decision: Revise Minor
10 Sep 20212nd Revision Received
11 Sep 2021Submission Checks Completed
11 Sep 2021Assigned to Editor
12 Sep 2021Editorial Decision: Accept