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

Advanced glycation endproducts (AGEs) may enhance vascular permeability in diabetic subjects. To test this hypothesis, AGEs were prepared in the prese nce of albumin (AGE-Alb). Control albumin (Alb) and AGE-Alb were then label ed with FITC (fluoresceinisothiocyanate) and injected i.v. into anesthetize d 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 measu red by direct intravital microscopy of the hamster cheek pouch preparations in fluorescent light and recorded as number of sites (=leaks) with extrava sation of FITC-labeled albumin in postcapillary venules. No changes were se en 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) befor e and at 30 and 60 min after FITC-Alb-injection and histamine application w as 257 +/- 6 (SEM), 243 +/- 6 and 231 +/- 6 leaks/cm(2) in the FITC-Alb-gro up and 258 +/- 6 (SEM), 302 +/- 12 and 316 +/- 11 leaks/cm(2) in the FITC-A GE-Alb-group, respectively, (P < 0.05 at 30 and 60 min). Similar results we re seen with bradykinin. Our conclusions showed that i.v.-injected AGEs aug mented the histamine- and bradykinin-induced increase in vascular permeabil ity by 34% and 46%. (Journal of Diabetes and Its Complications 13;4:187-190 , 1999.) (C) 1999 Elsevier Science Inc.