Catalase has negligible inhibitory effects on endothelium-dependent relaxations in mouse isolated aorta and small mesenteric artery

Anthie Ellis, Malarvannan Pannirselvam, Todd J. Anderson, Chris R. Triggle

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Abstract

1. The current study examined the hypothesis that endothelial production of hydrogen peroxide (H 2O 2) mediates relaxations to acetylcholine (ACh) in aorta and small mesenteric arteries (SMA) from mice. 2. Relaxations to ACh (0.01-10 μM) and H 2O 2 (0.1-1000 μM) were produced in aorta and SMA isolated from wild-type C57BL/6 mice and type II diabetic mice (db/db). In SMA, relaxations to ACh were produced in the presence of N ω-nitro-L-arginine methyl ester (100 μM) and indomethacin (Indo, 10 μM). 3. 1-H[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one (10 μM) significantly reduced ACh-induced relaxations in SMA, abolished responses in aorta, but had no effect on relaxations induced by H 2O 2. Catalase (2500 U ml -1) abolished responses to H 2O 2, but did not alter relaxations to ACh in the SMA and only caused a small rightward shift in responses to ACh in the aorta. 4. ACh-, but not H 2O 2-, mediated relaxations were significantly reduced by tetraethylammonium (10 mM). the combination of apamin (1 μM) and charybdotoxin (100 nM), and 25 mM potassium chloride (KCl). Higher KCl (60 mM) abolished relaxations to both ACh and H 2O 2. Polyethylene glycolated superoxide dismutase (100 U ml -1), the catalase inhibitor 3-amino-1,2,4-triazole (3-AT, 50 mM) and treatment with the copper chelator diethyldithiolcarbamate (3 mM) did not affect relaxations to ACh. 5. H 2O 2-induced relaxations were endothelium-independent and were not affected by ethylene diamine tetraacetic acid (EDTA 0.067 mM), 4-aminopyridine (1 mM), ouabain (100 μM) and barium (30 μM), 3-AT or Indo. 6. Although the data from this study show that H 2O 2 dilates vessels, they do not support the notion that H 2O 2 mediates endothelium-dependent relaxations to ACh in either aorta or SMA from mice.

Original languageEnglish
Pages (from-to)1193-1200
Number of pages8
JournalBritish Journal of Pharmacology
Volume140
Issue number7
DOIs
Publication statusPublished - 1 Dec 2003

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Keywords

  • Endothelium
  • Endothelium-derived hyperpolarizing factor (EDHF)
  • Hydrogen peroxide (H O )
  • Relaxation
  • Small mesenteric arteries (SMA)

ASJC Scopus subject areas

  • Pharmacology

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