Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes. Cardiovasc Res 2000 Aug 18;47(3):595-601
Date
08/30/2000Pubmed ID
10963732DOI
10.1016/s0008-6363(00)00094-8Scopus ID
2-s2.0-0342573147 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
UNLABELLED: 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 microM, 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 microM: 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.
Author List
Ammar RF Jr, Gutterman DD, Brooks LA, Dellsperger KCMESH terms used to index this publication - Major topics in bold
AcetylcholineAdenosine
Alloxan
Analysis of Variance
Animals
Arterioles
Catalase
Coronary Vessels
Diabetes Mellitus, Experimental
Dogs
Dose-Response Relationship, Drug
Endothelium, Vascular
Enzyme Inhibitors
Free Radical Scavengers
Muscle, Smooth, Vascular
Nitric Oxide Synthase
Nitroprusside
Superoxide Dismutase
Vasodilator Agents
