[Advanced glycation end products are involved in microvascular permeability changes observed in microcirculation of diabetic rats in vivo].
OBJECTIVE
Since chronic hyperglycemia leads to Advanced Glycation End Products (AGE) formation, we were interested in its involvement in changes in microvascular permeability during diabetes.


METHODS
Intravital microscopy was used to study changes in microvascular permeability during diabetes. The extravasation of a fluorescent macromolecular tracer (FITC-Albumin) was measured for one hour and, after computer-aided image analysis, was expressed as variations of normalized grey levels (arbitrary units).


RESULTS
The extravasation of the tracer was increased in diabetic rats. An intravenous bolus of s-RAGE (extracellular domain of the AGE receptor) inhibits dose-dependently this increase (fig. 1). The increase of the extravasation of the macromolecular tracer can be inhibited when s-RAGE are administered 1 and 3 hours before the experiment, but not when administered 1/4 hour and 12 hours before experiment (fig. 2). Administration of antibodies against AGE receptors also inhibits the increase of permeability observed in diabetic rats (fig. 3).


CONCLUSIONS
AGE interaction with their receptor is responsible for an increase in microvascular permeability.
Bonnardel-Phu
E
E
Laboratoire d'Etude de la Microcirculation, Département de Biophysique, Hôpital F. Widal. 200, rue du Faubourg Saint-Denis, 75475 Paris Cedex 10.
Wautier
J L
JL
Vicaut
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005119:Extravasation of Diagnostic and Therapeutic Materials; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D017127:Glycation End Products, Advanced / Q000276:immunology / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D008833:Microcirculation; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D017127:Glycation End Products, Advanced; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate