Vascular permeability increase as induced by histamine or bradykinin is enhanced by advanced glycation endproducts (AGEs).

Abstract Advanced glycation endproducts (AGEs) may enhance vascular permeability in diabetic subjects. To test this hypothesis, AGEs were prepared in the presence of albumin (AGE-Alb). Control albumin (Alb) and AGE-Alb were then labeled with FITC (fluoresceinisothiocyanate) and injected i.v. into anesthetized hamsters at a dose of 7 mg/100 g B.W. Normal hamsters were given FITC-Alb or FITC-AGE-Alb and FITC-dextran. Vascular permeability changes were measured by direct intravital microscopy of the hamster cheek pouch preparations in fluorescent light and recorded as number of sites (=leaks) with extravasation of FITC-labeled albumin in postcapillary venules. No changes were seen during 1 hour after i.v. injection of FITC-Alb or FITC-AGE-Alb. Repeated local application of histamine 5·10 −6 M or bradykinin 5·10 −7 M to the cheek pouch for 5 min with 30-min intervals induced reversible increases in vascular permeability in all hamsters. Maximal number of leaks/cm 2 before and at 30 and 60 min after FITC-Alb-injection and histamine application was 257 ± 6 (SEM), 243 ± 6 and 231 ± 6 leaks/cm 2 in the FITC-Alb-group and 258 ± 6 (SEM), 302 ± 12 and 316 ± 11 leaks/cm 2 in the FITC-AGE-Alb-group, respectively, ( P