Amelioration by L-arginine of a dysfunctional arginine/nitric oxide pathway in diabetic endothelium.
Defective endothelium-dependent relaxation in diabetic blood vessels may be regulated at the site of synthesis. We tested the hypothesis that acute administration of L-arginine (L-Arg) as substrate for endothelium-derived relaxing factor (EDRF) would normalize defective relaxation to acetylcholine (ACh) in streptozotocin-induced diabetic rat aortic rings. Plasma concentrations of basic amino acids (e.g., arginine, lysine, and histidine) were significantly reduced by diabetes, but variable results (increased, decreased, or no change) were observed in plasma concentrations of neutral amino acids. Endothelium-dependent relaxation to ACh (but not calcium ionophore A23187) was impaired in diabetic rings. Relaxation to nitroglycerin (NTG) was not altered. Pretreatment with L-nitroarginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, blocked the relaxation to ACh and A23187 but not relaxation to NTG in both control and diabetic rings. Pretreatment with 3 mM L-Arg (but not D-Arg) potentiated the relaxation to ACh in diabetic rings. L-Arg had no effect on ACh-induced relaxation in control rings or on relaxation to NTG in control or diabetic rings. A mechanism for impaired endothelium-dependent relaxation to ACh in diabetic aorta may arise from a defect in utilization of L-Arg by NO synthase for production of EDRF/NO.
Pieper
G M
GM
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
Peltier
B A
BA
D000109:Acetylcholine / Q000494:pharmacology; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester