title: 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 x 10(6) M or bradykinin 5 x 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/cm2 before and at 30 and 60 min after FITC-Alb-injection and histamine application was 257 +/- 6 (SEM), 243 +/- 6 and 231 +/- 6 leaks/cm2 in the FITC-Alb-group and 258 + 6 (SEM), 302 +/- 12 and 316 +/- 11 leaks/cm2 in the FITCAGE-Alb-group, respectively, (P < 0.05 at 30 and 60 min). Similar results were seen with bradykinin. Our conclusions showed that i.v.-injected AGEs augmented the histamine- and bradykinin-induced increase in vascular permeability by 34% and 46%.
authors.affiliation: Instituto do Coração, Universidade de São Paulo, SP, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Svensjö
authors.forename: F
authors.initials: F
authors.lastname: Cyrino
authors.forename: E
authors.initials: E
authors.lastname: Michoud
authors.forename: D
authors.initials: D
authors.lastname: Ruggiero
authors.forename: E
authors.initials: E
authors.lastname: Bouskela
authors.forename: N
authors.initials: N
authors.lastname: Wiernsperger
mesh_terms: D000418:Albumins; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D003911:Dextrans; D004357:Drug Synergism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000098:blood supply / Q000187:drug effects
chemical_list: D000418:Albumins; D003911:Dextrans; D005456:Fluorescent Dyes; D017127:Glycation End Products, Advanced; C015219:fluorescein isothiocyanate dextran; D006632:Histamine; D016650:Fluorescein-5-isothiocyanate; D001920:Bradykinin