© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes
aVA Medical Center, Highway 6 West, Iowa City, IA 52246, USA
bDepartment of Internal Medicine and the Cardiovascular Center, University of Iowa College of Medicine, Iowa City, IA 52242, USA
* Corresponding author. Tel.: +1-319-339-7102; fax: +1-319-339-7135 kevin.dellsperger{at}med.va.gov
Previous studies have demonstrated that vascular responses to acetylcholine (ACh) are impaired in diabetes mellitus (DM). Objective: Since reactive oxygen species (ROS) generation is increased in various disease states including DM, and a direct reaction between nitric oxide (NO) and superoxide anion has been demonstrated, we tested the hypothesis that inhibition of ROS will restore coronary microvascular responses to ACh in a dog model of DM (alloxan 60 mg/kg, i.v., 1 week prior to study). Methods: Changes in coronary microvascular diameters in diabetic (blood glucose >200 mg%) and normal animals to ACh (1–100 µM, topically) in the presence and absence of superoxide 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 microvascular dilation was impaired when compared to normal animals (ACh 100 µM: DM=25±5%; normal=64±13%, P<0.05). Topical application of SOD (250 U/ml) and catalase (250 U/ml) restored to normal ACh induced coronary microvascular responses in DM while having no affect in normal animals. Responses to adenosine and nitroprusside were not different between normal and diabetic groups. Conclusions: These data provide direct evidence that oxygen-derived free radicals contribute to impaired endothelium-dependent coronary arteriolar dilation in diabetic dogs in vivo.
KEYWORDS Diabetes; Coronary circulation; Free radicals; Microcirculation; Acetylcholine; Endothelial function
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