In resistance arteries from patients with cardiovascular disease, endothelium-dependent relaxations are mediated by NOS and sGC but not by NO, HNO, or H2O2, and continue during excessive oxidative stress.
In resistance arteries from patients with cardiovascular disease, endothelium-dependent relaxations involve NOS and sGC but do not appear to be mediated by NO, HNO, or H2O2, and persist during oxidative stress.
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 H 2 O 2 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 H 2 O 2 , although NOS and sGC can be involved. These vasodilator responses continue during excessive oxidative stress.
Matthies et al. (Wed,) conducted a other in Cardiovascular disease. Bradykinin was evaluated on Endothelium-dependent relaxation. In resistance arteries from patients with cardiovascular disease, endothelium-dependent relaxations are mediated by NOS and sGC but not by NO, HNO, or H2O2, and continue during excessive oxidative stress.