Short- and long-term modulation of microvascular responses in streptozotocin-induced diabetic rats by glycosylated products.
OBJECTIVE
This study aimed to determine the role of early and late glycation products in modulating inflammation in early diabetes.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Amadori and anti-AGE agents enhance peripheral vascular responses in diabetes and may ameliorate microvascular damage.
Bassirat
Maryam
M
Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Victoria, Australia. mbassirat@medstv.unimelb.edu.au
Khalil
Zeinab
Z
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004195:Disease Models, Animal; D005122:Exudates and Transudates / Q000187:drug effects; D005528:Foot / Q000098:blood supply; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000502:physiology*; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D017127:Glycation End Products, Advanced; D006146:Guanidines; D010455:Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C004479:pimagedine