Oxygen-derived free radicals mediate endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes.
OBJECTIVE
The present experiments were designed to study the contribution of oxygen-derived free radicals to endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes.


METHODS
Rings with and without endothelium were suspended in organ chambers for isometric tension recording. The production of oxygen-derived free radicals in the endothelium was measured with 2',7'-dichlorodihydrofluorescein diacetate using confocal microscopy. The presence of protein was measured by western blotting.


RESULTS
In the presence of L-NAME, the calcium ionophore A23187 induced larger endothelium-dependent contractions in femoral arteries from diabetic rats. Tiron, catalase, deferoxamine and MnTMPyP, but not superoxide dismutase reduced the response, suggesting that oxygen-derived free radicals are involved in the endothelium-dependent contraction. In the presence of L-NAME, A23187 increased the fluorescence signal in femoral arteries from streptozotocin-treated, but not in those from control rats, confirming that the production of oxygen-derived free radicals contributes to the enhanced endothelium-dependent contractions in diabetes. Exogenous H2O2 caused contractions in femoral arterial rings without endothelium which were reduced by deferoxamine, indicating that hydroxyl radicals contract vascular smooth muscle and thus could be an endothelium-derived contracting factor in diabetes. The reduced presence of Mn-SOD and the decreased activity of catalase in femoral arteries from streptozotocin-treated rats demonstrated the presence of a redox abnormality in arteries from rats with diabetes.


CONCLUSIONS
These findings suggest that the redox abnormality resulting from diabetes increases oxidative stress which facilitates and/or causes endothelium-dependent contractions.
Shi
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Department of Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
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K-F
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Man
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Vanhoutte
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PM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D009924:Organ Culture Techniques; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D000975:Antioxidants; D004791:Enzyme Inhibitors; D016877:Oxidants; D017382:Reactive Oxygen Species; D000001:Calcimycin; D013311:Streptozocin; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase