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 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.
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.