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Aim The effect of 8 weeks' streptozotocin (STZ)-induced diabetes and aminoguanidine (AMNG), the inhibitor of advanced glycosylation reaction, treatment on arteriolar reactivity to vasoactive substances was investigated in vitro. Materials and Methods Studies were performed in untreated control rats (n=10), mg/kg i.v.) diabetic rats (n=10), AMNG-treated (600mg/1 given in drinking water throughout 8 weeks) control rats (n=10) and AMNG-treated (600mg/1 given in drinking water, beginning at 72h after STZ and throughout 8 weeks of diabetes) diabetic rats (n=10). Results are expressed as the mean 4-s.e. Relaxant responses are expressed as a percentage (%) relaxation of noradrenaline-induced tone. Statistical comparisons were made by one-way analysis of variance (ANOVA) followed by Tukey-Kramer multiple comparisons test.Results 1. The decreased body weights (205 4-6g) and increased blood glucose levels (583 4-8 mg/dl) of diabetic rats were partially restored by treatment of aminoguanidine (253 4-6 g, p < 0.05 and 480 4-14 mg/ dl, p < 0.001, respectively). 2. Diabetes caused a 71% deficit in maximal endothelium-dependent relaxation to acetylcholine for noradrenaline precontracted aortas (p<0.001). AMNG treatment prevented the diabetes-induced impairment in endothelium dependent relaxation (58 4-8%) to acetylcholine, maximum relaxation remaining in the non-diabetic range (78 4-4% MATERIALS AND METHODS AnimalsAlbino Wistar rats were bred in our laboratory and nourished ad libitum with standart pellet diet and had free access to tap water.Adult male and female Wistar rats (n=40), weighing 200-300g, were divided into four groups:(i) Normal Control (= NC) (n 10),(ii) STZ-diabetic group (= DC) (n 10), Aortic StripsRats were sacrified by stunning followed by decapitation. A segment (3-5cm) of thoracic aorta was removed and placed in an ice-cold Krebs-Ringer solution (KRS) of the following composition (mmol/L): NaC1 (118), KC1 (4.7), CaC12 (2.5), MgSO4.7H20 (1.2), KH2PO4 (1.2), NaHCO3 and glucose (11.1) and then trimmed free of adhering fat and connective tissue and cut into rings of 3 mm width. The rings were opened by cutting the vessels longitudinally. Subsequently, they were fixed with stainless steel clips at both ends and then placed in 20 ml EFFECT Table I.The body weights of diabetic rats (205 4-7 g) were significantly lower than NC (p < 0.001), AG-C (p < 0.001) and AG+D (p < 0.05) rats.Eight weeks after injection, all rats treated with STZ exhibited severe hyperglycaemia and their blood glucose levels (583 4-8mg/dl) were significantly higher than those of NC (p < 0.001), AG-C (p < 0.001) and AG+D (p < 0.001)rats.Water intakes and AG dosages were also shown in Table I. Agonist-induced ContractionsThe contractile responses of aortic strips from all groups are shown in Tables II and III [10-14, 19, 20] response.It has been shown that hyperglycaemia which is one of the most important markers of diabetes, caused tissue damage with several mechanisms, including advanced glycation end product (AGE) [39,40] The...

This study was performed to test whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to obesity and obesity complications including decrement in insulin sensitivity and adiponectin levels, dyslipidemia and low-grade inflammation. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations were analyzed by HPLC in 17 overweight (BMI > or = 25 kg/m2) and 40 obese (BMI > or = 30 kg/m2) premenopausal women. Age-matched healthy women were studied as controls. Obesity did not give rise to a significant change in circulating ADMA levels but reduced in SDMA levels. As compared with control subjects (0.441 +/- 0.102 microM), ADMA values in overweight and obese subjects were found to be as 0.412 +/- 0.102 and 0.436 +/- 0.093, respectively. No Pearson's association of ADMA with relevant risk variables for cardiovascular disease, including blood pressure, insulin sensitivity, inflammatory markers, lipid and adiponectin levels. However, in linear regression analysis, BMI, diastolic blood pressure, glucose, insulin, and IL-8 emerged as significant predictors of ADMA. In spite of obese women have elevated hs-CRP, triglyceride levels and decreased insulin sensitivity, adiponectin and HDL-cholesterol levels, all of which is closely linked risk factors for cardiovascular disease, circulating ADMA levels remained unchanged in obese individuals as compared with controls.