<i>L</i>-Arginine Supplementation Prevents the Development of Endothelial Dysfunction in Hyperglycaemia

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.

Antihyperglycemic and antioxidative potential of Matricaria chamomilla L. in streptozotocin-induced diabetic rats

“…An antioxidative property of NO has been reported by some investigators [23,24]. Furthermore, some studies revealed the protective effects of the NO-generating compounds L-arginine and sodium nitroprusside in STZdiabetic rats [25,26]. NO seems to be a potential antioxidant in the present study.…”

Hyperglycemia Reduces Survival and Impairs Function of Circulating Blood-Derived Progenitor Cells

“…Furthermore, in vitro studies on hyperglycemia assessing various characteristics of different cell types found effects in the hyperglycemia group, whereas no effects were described in both osmotic control groups, neither L-glucose-supplemented nor mannitol-supplemented. 23,24 …”

Nitric oxide and cardiovascular risk factors

“…Dietary supplementation with L-arginine (a substrate of NOS) seems able to rebalance NO production on the dysfunctional endothelium, stimulating NOS activity both directly and indirectly: antagonizing the effects of ADMA and reducing endothelin-1 synthesis (41). Lerman et al (42) found a significant improvement in endothelial function in patients with coronary artery disease after 6 months of L-arginine supplementation.…”

“…Lerman et al (42) found a significant improvement in endothelial function in patients with coronary artery disease after 6 months of L-arginine supplementation. Treated patients showed a better vasodilatory response after acetylcholine induced contraction and reduced endothelin-1 plasmatic levels.…”