title: Blockade of early and late retinal biochemical alterations associated with diabetes development by the selective bradykinin B1 receptor antagonist R-954.
abstract: The chronic hyperglycemia measured alongside diabetes development is associated with significant long-term damage and failure of various organs. In the present study it was shown that hyperglycemia induced early and long term increases in nitric oxide (NO) levels, kallikrein activity and vascular capillary permeability measured as plasma extravasation, and decreases of Na/K ATPase activity in diabetic rat retina 4 and 12 weeks after streptozotocin (STZ) injection. Treatment of the animals for 5 consecutive days with a novel selective bradykinin B(1) receptor (BKB(1)-R) antagonist R-954 (2mg/kg s.c) at the end of the 4 and 12 week periods highly reduced NO, kallikrein and capillary permeability and increased Na/K ATPase activity in the retina. These results suggest that the BKB(1)-R receptor subtype is over-expressed during the streptozotocin-induced development of diabetes in rat retina as evidenced by the inhibitory effects of the BKB(1)-R antagonist R-954 on NO, kallikrein and vascular permeability increases as well as Na/K ATPase decreases. The beneficial role of the BKB(1)-R antagonist R-954 for the treatment of the diabetic retinopathy is also suggested.
authors.affiliation: Departamento de Biologia, Universidad Argentina John F Kennedy, Buenos Aires, Argentina. ocatan50@aol.com
authors.forename: Orlando
authors.initials: O
authors.lastname: Catanzaro
authors.forename: Emilio
authors.initials: E
authors.lastname: Labal
authors.forename: Ana
authors.initials: A
authors.lastname: Andornino
authors.forename: Jorgelina Aria
authors.initials: JA
authors.lastname: Capponi
authors.forename: Irene
authors.initials: I
authors.lastname: Di Martino
authors.forename: Pierre
authors.initials: P
authors.lastname: Sirois
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065169:Bradykinin B1 Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: C476306:Ac-Orn-(Oic2, alpha-MePhe5, D-betaNal7, Ile8)desArg9-bradykinin; D065169:Bradykinin B1 Receptor Antagonists; D007004:Hypoglycemic Agents; D043783:Receptor, Bradykinin B1; D009569:Nitric Oxide; D007610:Kallikreins; D000254:Sodium-Potassium-Exchanging ATPase; D001920:Bradykinin