title: 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 effect 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 final 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 microM) 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 microM) in endothelium-denuded rings. 5. Incubation with 3-amino-1,2,4-triazole (50 mM, 90 min, followed by washout) had no effect 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 final 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.
authors.affiliation: Clinical Research Initiative, University of Glasgow.
authors.forename: K B
authors.initials: KB
authors.lastname: Mian
authors.forename: W
authors.initials: W
authors.lastname: Martin
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D002374:Catalase / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006540:Herbicides / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D006540:Herbicides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D000109:Acetylcholine; D000640:Amitrole