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

This study aimed to determine the role of early and late glycation products in modulating inflammation in early diabetes.Sprague-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.The base of a vacuum-induced blister raised on the hind paw was perfused with substance P (SP, 1 microM) and sodium nitroprusside (SNP, 100 microM). 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 microg/ml) were individually perfused prior to SP.In 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.Amadori and anti-AGE agents enhance peripheral vascular responses in diabetes and may ameliorate microvascular damage.