L-Arginine Supplementation Prevents the Development of Endothelial Dysfunction in HyperglycaemiaKabat A. · Dhein S.
aInstitute of Pharmacology, University of Halle, Faculty of Medicine, Halle, and bUniversity of Leipzig, Heart Centre Leipzig, Clinic for Cardiac Surgery, Leipzig, Germany
Diabetes mellitus leads to the development of endothelial dysfunction which finally contributes to diabetic angiopathy. We investigated the effects of hyperglycaemia on nitric oxide (NO) liberation and a possible influence of L-arginine supplementation. Porcine endothelial aortic cells (PAEC) were cultured in Medium 199 containing 0.33 mmol/l L-arginine. During the entire third culture passage (= 4 days) cells were either exposed to 5 or 20 mmol/l D-glucose with or without additional 3 mmol/l L-arginine. For osmotic control, cells were exposed to 15 mmol/l mannitol. NO liberation was measured under basal conditions and after stimulation with 1 mmol/l ATP using the spectrophotometrical methemoglobin assay. Cells released 35 ± 8 pmol NO/1 × 106 cells/10 min under basal conditions while hyperglycaemia led to a significant reduction in NO release to 16 ± 6 pmol/1 × 106 cells/10 min. In osmotic control, NO release was unchanged (37 ± 10 pmol/1 × 106 cells/10 min). Stimulation with 1 mmol/l ATP led to a significant increase in NO release to 103 ± 11 pmol/1 × 106 cells/10 min (normoglycaemia) which was unchanged in osmotic controls. Under normoglycaemic conditions, additional L-arginine supplementation did not influence NO release from PAEC. In hyperglycaemia (0.33 mmol/l L-arginine) ATP stimulated NO release was reduced (48 ± 8 pmol/1 × 106 cells/10 min, p < 0.05), which was completely prevented by 3 mmol/l L-arginine treatment (98 ± 15 pmol/ 1 × 106 cells/10 min). Hyperglycaemia (but not enhanced osmotic pressure) leads to endothelial dysfunction with reduced NO release which is completely prevented by L-arginine. L-Arginine utilisation may be impaired in hyperglycaemia and L-arginine supplementation might be an interesting additional therapeutic tool in diabetic patients.
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