Participation of reactive oxygen species in diabetes-induced endothelial dysfunction.
OBJECTIVE
In the present study, the relationship between diabetes-induced hyperglycemia, reactive oxygen species production and endothelium-mediated arterial function was examined. The effect of antioxidant on the reactive oxygen species induced damage was tested.


METHODS
Diabetes was induced by streptozotocin (STZ), 3 x 30 mg/kg i.p., administered on three consecutive days. After 10 weeks of diabetes, the functional state of the endothelium of the aorta was tested, endothelemia evaluation was performed and systolic blood pressure was measured. Reactive oxygen species (ROS) formation in blood and the aorta was measured using luminol-enhanced chemiluminescence (CL). Levels of reduced glutathione (GSH) were determined in the aorta, kidney, and plasma. To study the involvement of hyperglycemia in functional impairment of the endothelium, aortal rings incubated in solution with high glucose concentration were tested in in vitro experiments.


RESULTS
After 10 weeks of diabetes, endothelial injury was observed, exhibited by diminished endothelium-dependent relaxation of the aorta, increased endothelemia and by elevated systolic blood pressure. Using luminol-enhanced CL, a significant increase of ROS production was found in arterial tissue and blood. GSH levels were significantly increased in the kidney, while there were no GSH changes in plasma and the aorta. Incubation of aortic rings in solution with high glucose concentration led to impairment of endothelium-dependent relaxation. The synthetic antioxidant SMe1EC2 was able to restore reduced endothelium-mediated relaxation.


CONCLUSIONS
Our results suggest an important role of hyperglycemia-induced ROS production in mediating endothelial dysfunction in experimental diabetes, confirmed by CL and the protective effect of the antioxidant SMe1EC2.
Zúrová-Nedelcevová
Jana
J
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia.
Navarová
Jana
J
Drábiková
Katarína
K
Jancinová
Viera
V
Petríková
Margita
M
Bernátová
Iveta
I
Kristová
Viera
V
Snirc
Vladimír
V
Nosál'ová
Viera
V
Sotníková
Ruzena
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology; D003925:Diabetic Angiopathies / Q000209:etiology*; D006943:Hyperglycemia / Q000150:complications; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000009:adverse effects* / Q000378:metabolism; D013311:Streptozocin; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D013311:Streptozocin; D000109:Acetylcholine