Dietary l-Arginine Supplementation Enhances Endothelial Nitric Oxide Synthesis in Streptozotocin-Induced Diabetic Rats

• Published in: The Journal of nutrition Vol. 134; no. 3; pp. 600 - 608
• Main Authors: Kohli, Ripla, Meininger, Cynthia J., Haynes, Tony E., Yan, Wene, Self, Jon T., Wu, Guoyao
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.03.2004; American Society for Nutritional Sciences
• Subjects: alanine; Alanine - pharmacology; Amino Acids; Amino Acids - blood; Animals; arginine; Arginine - pharmacology; Biological and medical sciences; biosynthesis; blood; blood glucose; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Weight; Body Weight - drug effects; Coronary Vessels; Coronary Vessels - physiopathology; diabetes; Diabetes Mellitus, Experimental; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Diet; Dietary Supplements; drinking water; drug effects; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; endothelial cells; Endothelium, Vascular; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Feeding. Feeding behavior; food intake; Fundamental and applied biological sciences. Psychology; glucose; homeostasis; insulin; Insulin - blood; Male; Medical sciences; metabolism; methylarginines; nitric oxide; Nitric Oxide - biosynthesis; nitrogen content; pharmacology; physiopathology; plasma cells; Rats; Rats, Sprague-Dawley; Reference Values; Vertebrates: anatomy and physiology, studies on body, several organs or systems; weight loss; BB; NO; nitric oxide; methylarginines; endothelial cells; arginine; SDMA; NMMA; STZ; ADMA; diabetes; BH4; Endocrinopathy; Endothelial cell; Nutrition; Rat; Diabetes mellitus; Rodentia; Biosynthesis; Vertebrata; Mammalia; Arginine; Animal; Nitric oxide; Supplementation; Streptozotocin
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/134.3.600

This study tested the hypothesis that dietary arginine supplementation increases endothelial tetrahydrobiopterin (BH4) availability for nitric oxide (NO) synthesis in diabetic rats. Streptozotocin-induced diabetic rats either were given unrestricted access to a casein-based diet (Expt. 1) or were pair-fed the diet on the basis of the food intake per kg of body weight of nondiabetic rats (Expt. 2). Beginning 1 d after vehicle or streptozotocin injection, arginine-HCl (1.51%) or alanine (isonitrogenous control, 2.55%) was added daily to the drinking water for nondiabetic rats, whereas concentrations were adjusted (0.43% arginine-HCl and 0.73% alanine) in the drinking water for diabetic rats (which consumed more water) to ensure isonitrogenous provision. At 2 wk after the initiation of arginine supplementation, coronary endothelial cells and plasma were obtained for the measurement of NO synthesis and metabolites. In both experiments, plasma and endothelial concentrations of NG-monomethylarginine, asymmetric dimethylarginine, and symmetric dimethylarginine increased, but those of arginine as well as endothelial BH4 availability and NO synthesis decreased in diabetic rats, compared with nondiabetic rats. In both diabetic and nondiabetic rats, arginine supplementation increased plasma concentrations of arginine and insulin, endothelial concentrations of arginine and BH4, and endothelial NO synthesis, but did not affect plasma and endothelial concentrations of methylarginines or plasma concentrations of homocysteine. Dietary arginine supplementation or provision of a BH4 precursor normalized endothelial NO synthesis in diabetic rats. Arginine supplementation did not affect plasma glucose levels in nondiabetic rats, but reduced body weight loss and plasma glucose levels in diabetic rats. Thus, dietary L-arginine supplementation stimulates endothelial NO synthesis by increasing BH4 provision, which is beneficial for vascular function and glucose homeostasis in diabetic subjects.