Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes.
This study was designed to determine the relationship between elevated levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and metabolic control in rats with streptozotocin-induced diabetes. Serum levels of ADMA were measured by high-performance liquid chromatography at 8 weeks after diabetes was induced. Endothelium-dependent relaxation to acetylcholine was tested in aortic rings from nondiabetic age-matched control, untreated diabetic, and insulin-treated diabetic rats to evaluate endothelial function. Serum concentrations of glucose, glycosylated serum protein, and malondialdehyde were examined to estimate metabolic control. Serum levels of ADMA increased dramatically in untreated diabetic rats compared with control rats. This elevation in ADMA levels was accompanied by impairment of the endothelium-dependent relaxation response to acetylcholine in aortic rings. Long-term insulin treatment not only prevented the elevation of serum ADMA levels, but also improved the impairment of endothelium-dependent relaxation in diabetic rats. Serum levels of glucose, glycosylated serum protein, and malondialdehyde were significantly increased in parallel with the elevation of ADMA in untreated diabetic rats compared with control rats. These parameters were normalized after diabetic rats received insulin treatment for 8 weeks. These results provide the first evidence that an elevation in the concentration of ADMA in rats with streptozotocin-induced diabetes is closely related to metabolic control of the disease.
Xiong
Yan
Y
Department of Pharmacology, Basic and Clinic Pharmacological Institute, Xiang-ya Medical College, Central South University, 88 Xiang-ya Road, Changsha 410 078 Hunan, P.R. China. xiongyan@yahoo.com
Fu
Yun-feng
YF
Fu
Si-hai
SH
Zhou
Hong-hao
HH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001786:Blood Glucose / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000097:blood*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase