Effect of superoxide dismutase on endothelium-dependent relaxation of aorta from endotoxin-treated rabbits.
To assess the protective effect of superoxide dismutase (SOD) on the endothelium of aorta in endotoxaemia, we investigated the production of endothelium-derived relaxing factor in aorta obtained from endotoxin-treated rabbits concomitantly receiving SOD or not. Thirty-two male Japanese white rabbits were randomly divided into four groups (n = 8 for each group): one group receiving saline as a placebo, a second receiving 5 mg/kg endotoxin intravenously, a third receiving 5 mg/kg endotoxin intravenously plus SOD, and a fourth receiving SOD alone. SOD was injected intravenously at a dose of 10,000 U/kg before the endotoxin and was infused continuously at a rate of 15,000 units/kg/h throughout the experiment. The tension of the aorta was recorded in vitro 6 h after the start of in vivo treatment with endotoxin or saline. In the aorta of rabbits receiving endotoxin alone, acetylcholine-induced relaxation was reduced by 50%. The SOD fully restored the reduction of acetylcholine-induced relaxation by endotoxin. Histological studies using photomicroscopy revealed endothelial damage in the endotoxin-treated aorta, which was attenuated in the SOD-treated group. These data suggest that intravenous SOD may be an effective treatment for unstable haemodynamics in endotoxaemia.
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
H
H
Yaku
K
K
Mikawa
K
K
Nishina
N
N
Maekawa
H
H
Obara
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology*
D004731:Endotoxins; D009599:Nitroprusside; D013482:Superoxide Dismutase; D000109:Acetylcholine