SHORT-TERM ORAL-ADMINISTRATION OF L-ARGININE REVERSES DEFECTIVE ENDOTHELIUM-DEPENDENT RELAXATION AND CGMP GENERATION IN DIABETES

In the present study, we evaluated whether acute dietary supplementati on with L-arginine in vivo could reverse the defective endothelium-dep endent relaxation in diabetic blood vessels assessed ex vivo. At 8 wee ks of diabetes, streptozotocin-induced diabetic rats were given 1.25% L-arginine in drinking water 3 days prior to isolation of aortic rings for evaluation ex vivo. Plasma arginine concentration was reduced by diabetes but restored to normal in diabetic rats receiving dietary L-a rginine. In norepinephrine-contracted rings, relaxation to acetylcholi ne but not to nitroglycerin was reduced by diabetes. Dietary treatment with L-arginine restored relaxation to acetylcholine without altering relaxation to nitroglycerin and restored the defect in acetylcholine stimulated cGMP generation. These data suggest that the substrate for nitric oxide synthesis by the endothelium is likely to be limited in d iabetes but can be overcome by dietary supplementation with L-arginine .