Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes

Previous studies have demonstrated that vascular responses to acetylcholine (ACh) are impaired in diabetes mellitus (DM). Objective: Since reactive ox ygen species (ROS) generation is increased in various disease states includ ing DM, and a direct reaction between nitric oxide (NO) and superoxide anio n has been demonstrated, we tested the hypothesis that inhibition of ROS wi ll restore coronary microvascular responses to ACh in a dog model of DM (al loxan 60 mg/kg, i.v., 1 week prior to study). Methods: Changes in coronary microvascular diameters in diabetic (blood glucose >200 mg%) and normal ani mals to ACh (1-100 mu M, topically) in the presence and absence of superoxi de dismutase and catalase were measured using intravital microscopy coupled to stroboscopic epi-illumination and jet ventilation. Results: In diabetic animals in the absence of ROS scavengers, ACh induced coronary microvascul ar dilation was impaired when compared to normal animals (ACh 100 mu M: DM= 25+/-5%; normal=64+/-13%, P<0.05). Topical application of SOD (250 U/ml) an d catalase (250 U/ml) restored to normal ACh induced coronary microvascular responses in DM while having no affect in normal animals. Responses to ade nosine and nitroprusside were not different between normal and diabetic gro ups. Conclusions: These data provide direct evidence that oxygen-derived fr ee radicals contribute to impaired endothelium-dependent coronary arteriola r dilation in diabetic dogs in vivo. (C) 2000 Elsevier Science B.V. All rig hts reserved.