Enhanced dermal and retinal vascular permeability in streptozotocin-induced type 1 diabetes in Wistar rats: blockade with a selective bradykinin B1 receptor antagonist.
The vascular complications associated with type 1 diabetes are to some extent related to the dysfunction of the endothelium leading to an increased vascular permeability and plasma extravasation in the surrounding tissues. The various micro- and macro-vascular complications of diabetes develop over time, leading to nephropathy, retinopathy and neuropathy and cardiomyopathy. In the present study, the effect of a novel selective bradykinin B1 receptor (BKB1-R) antagonist, R-954, was investigated on the changes of vascular permeability in the skin and retina of streptozotocin (STZ)-induced type 1 diabetic rats. Plasma extravasation increased in the skin and retina of STZ-diabetic rats after 1 week and persisted over 4 weeks following STZ injection. Acute treatment with R-954 (2 mg/kg, bolus s.c.) highly reduced the elevated vascular permeability in both 1- and 4-week STZ-diabetic rats. These results showed that the inducible BKB1-R subtype modulates the vascular permeability of the skin and retina of type 1 diabetic rats and suggests that BKB1-R antagonists could have a beneficial role in diabetic neuropathy and retinopathy.
Lawson
Sibi R
SR
Institute of Pharmacology of Sherbrooke, School of Medicine, University of Sherbrooke, Sherbrooke, PQ, J1H 5N4, Canada.
Gabra
Bichoy H
BH
Guérin
Brigitte
B
Neugebauer
Witold
W
Nantel
François
F
Battistini
Bruno
B
Sirois
Pierre
P
D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D012160:Retina / Q000187:drug effects*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D013311:Streptozocin / Q000494:pharmacology
D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D013311:Streptozocin