Hydrogen peroxide‐induced impairment of reactivity in rat isolated aorta: potentiation by 3‐amino‐1,2,4‐triazole

Abstract

1 In this study the impairment induced by hydrogen peroxide of vascular reactivity and the role of endogenous catalase in protection against this impairment was assessed in isolated rings of rat aorta. 2 Incubation with hydrogen peroxide at 1 mM, but not at 0.1 mM, for 15, 30 or 60 min followed by washout depressed, in a time-dependent manner, the subsequent ability of endothelium-containing and endothelium-denuded rings to contract to phenylephrine. 3 Incubation with 3-amino-1,2,4-triazole (50 mM, 90 min, followed by washout) to inhibit endogenous catalase had no e ect by itself on subsequent phenylephrine-induced contraction. However, pretreatment with 3-amino-1,2,4-triazole did lead to a profound enhancement of the ability of hydrogen peroxide (1 mM, present for the ®nal 30 min of the 90 min incubation, followed by washout) to depress phenylephrine-induced contraction in both endothelium-containing and endothelium-denuded rings. 4 Incubation with hydrogen peroxide at 1 mM, but not at 0.1 mM, for 15, 30 or 60 min followed by washout inhibited, in a time-dependent manner, the subsequent ability of acetylcholine (10 nM ± 3 mM) to induce endothelium-dependent relaxation. Furthermore, incubation with hydrogen peroxide 1 mM (30 min, followed by washout) also inhibited relaxation induced by glyceryl trinitrate (1 ± 100 nM) or isoprenaline (10 nM ± 3 mM) in endothelium-denuded rings. 5 Incubation with 3-amino-1,2,4-triazole (50 mM, 90 min, followed by washout) had no e ect by itself on relaxation induced by acetylcholine, glyceryl trinitrate or isoprenaline. In contrast, pretreatment with 3-amino-1,2,4-triazole led to profound enhancement of the ability of hydrogen peroxide (1 mM, present for ®nal 30 min of the 90 min incubation) to block relaxation to acetylcholine, glyceryl trinitrate or isoprenaline. 6 On the basis of the actions of 3-amino-1,2,4-triazole, it is likely that endogenous catalase plays an important role in the protection of vascular reactivity of rat aorta against oxidant damage by high (1 mM) but not lower (0.1 mM) concentrations of hydrogen peroxide. The data are consistent with the promotion of non-selective damage to the vascular smooth muscle cells by hydrogen peroxide, but endothelial damage may also be sustained.

Hydrogen Peroxide Promotes Endothelial Dysfunction by Stimulating Multiple Sources of Superoxide Anion Radical Production and Decreasing Nitric Oxide Bioavailability

“…2B). These results suggest that consistent with previous reports [13,42], H 2 O 2 does not decrease eNOS activity in PAEC under conditions where ACh-induced increase in cellular cGMP is impaired.…”

“…The effect of H 2 O 2 on agonist-induced vessel relaxation remains unclear with some [42,43] though not all studies [44] reporting a diminished response to ACh. Pre-treatment of rabbit aortic rings with 10 µM H 2 O 2 had no significant effect on subsequent vessel relaxation elicited by ACh (Fig.…”

Endothelin-1-induced contraction in veins is independent of hydrogen peroxide

“…3D), suggesting that endogenous H 2 O 2 does not cause venous relaxation under these conditions. We were concerned that millimolar concentrations of H 2 O 2 would cause vessel injury because several groups reported observing reductions in contractility after exposure to H 2 O 2 (1 mM) (4,15,21). We compared initial NE (10 M) contraction in the vena cava at the beginning of an experiment to a subsequent NE (10 M) contraction after cumulative exogenous H 2 O 2 concentration response curves had been performed, and we considered H 2 O 2 -induced vessel injury to be a reduction in NE (10 M) contraction compared with the initial NE contraction.…”

Effet de l’huile d’argan sur la contractilité de l’aorte : susceptibilité au stress oxydatif

“…Chez des personnes saines, Derouiche et al [17] . Cette molécule est une espèce oxygénée réactive, générée au cours de diverses situations physiopathologiques [18] et altère la réactivité vasculaire [19]. Par ailleurs, Tanguy et al [20] ont démontré que l'incubation des anneaux d'aorte isolée avec le H 2 O 2 diminuait la réactivité vasculaire d'une manière dose-dépendante.…”