Short- and long-term modulation of microvascular responses in streptozotocin-induced diabetic rats by glycosylated products

ObjectiveThis study aimed to determine the role of early and late glycation products in modulating inflammation in early diabetes.MaterialsSprague–Dawley rats (130–170 g) were injected with streptozotocin (75 mg/kg, ip) and treated with daily aminoguanidine (AG, 25 mg/kg, ip) or vehicle for 2 or 4 weeks.MethodsThe base of a vacuum-induced blister raised on the hind paw was perfused with substance P (SP, 1 μM) and sodium nitroprusside (SNP, 100 μM). Changes in blood flow and plasma extravasation (PE) were measured. Amadori (1 mg/ml), advanced glycation end products (AGEs, 10 mg/ml), and anti-RAGE IgG (antibody against AGE receptors, 100 μg/ml) were individually perfused prior to SP.ResultsIn diabetic rats, responses to SNP and SP were reduced by 60% and 70%, respectively (P<.05). Amadori increased responses to SNP by 50% and 90% and to SP by 70% and 80% in control and diabetic rats, respectively (both P<.05). SP responses were significantly increased after anti-RAGE IgG (70%) or AG treatments (175%) with PE responses normalized.ConclusionAmadori and anti-AGE agents enhance peripheral vascular responses in diabetes and may ameliorate microvascular damage.