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

• Published in: British journal of pharmacology Vol. 179; no. 5; pp. 1049 - 1064
• Main Authors: Matthies, Maximilian, Rosenstand, Kristoffer, Nissen, Inger, Muitjens, Stan, Riber, Lars P., De Mey, Jo G. R., Bloksgaard, Maria
• Format: Journal Article
• Language: English
• Published: London Blackwell Publishing Ltd 01.03.2022
• Subjects: Anions; Arteries; Bioavailability; Biopsy; Bradykinin; Cardiovascular disease; Cardiovascular diseases; Catalase; coronary artery disease; Depolarization; Endothelins; endothelin‐1; Endothelium; Guanylate cyclase; Heart surgery; Hydrogen peroxide; Microvasculature; Nitric oxide; Nitric-oxide synthase; Oxidative stress; Patients; Pericardium; Reactive oxygen species; Superoxide anions; Superoxide dismutase; Vasodilation; Veins & arteries
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.15712

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. Endothelium‐dependent relaxations can be inhibited by L‐NAME and ODQ during depolarization‐induced contraction but not in the presence of endothelin‐1 (ET‐1). A role for NO, HNO or H2O2 could not be demonstrated. Alternative mechanisms seem to be involved. They do not depend on reactive oxygen species and are resistant to elevated levels of superoxide anions.