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Endothelial protective effect of stobadine on ischaemia/reperfusion-induced injury.

General physiology and biophysics

Acetylcholine, pharmacology, Animals, Anti-Arrhythmia Agents, Aorta, Abdominal, drug effects, physiology, physiopathology, Carbolines, Endothelium, Vascular, ultrastructure, In Vitro Techniques, Ischemia, Lipid Peroxidation, Male, Mitochondria, pathology, Muscle Contraction, Muscle, Smooth, Vascular, Nitroprusside, Norepinephrine, Rats, Rats, Wistar, Reperfusion Injury, prevention & control, Thiobarbituric Acid Reactive Substances, analysis, Vasoconstriction, Vasodilation

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      The aim of the present study was to evaluate the influence of the antioxidant stobadine on changes in the reactivity of the rat abdominal aorta induced by ischaemia and reperfusion (I/R). In anaesthetized male rats, in vivo ischaemia was elicited by occlusion of the abdominal aorta for 18 hours; reperfusion lasted 30 minutes. The aortal rings were taken from the reperfused portion. Decreased relaxant response to acetylcholine, as a consequence of endothelial injury, was seen after I/R. We also demonstrated I/R-induced reversible ultrastructural changes both in endothelial and smooth muscle cells, predominantly in the mitochondria. Lipid peroxidation was increased in homogenates of I/R aortae; the concentration of thiobarbituric acid reactive substances (TBARS) increased from a control value of 0.97 +/- 0.03 to 2.57 +/- 0.06 nmol/l/mg protein. Stobadine (2 mg/kg i.v., 5 minutes before starting reperfusion) protected the abdominal aorta against I/R-induced decrease of acetylcholine relaxation, and prevented changes in mitochondria and an increase of TBARS concentration. The protective effect of stobadine seems to be due to its antioxidant properties.

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