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Vol. 76, No. 4, 2006
Issue release date: April 2006
Pharmacology 2006;76:185–191
(DOI:10.1159/000091606)

L-Arginine Supplementation Prevents the Development of Endothelial Dysfunction in Hyperglycaemia

Kabat 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

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Abstract

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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