Enhanced dermal and retinal vascular permeability in streptozotocin-induced type 1 diabetes in Wistar rats: blockade with a selective bradykinin B1 receptor antagonist

Regul Pept. 2005 Jan 15;124(1-3):221-4. doi: 10.1016/j.regpep.2004.09.002.

Abstract

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.

MeSH terms

  • Animals
  • Bradykinin B1 Receptor Antagonists*
  • Capillary Permeability / drug effects*
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / metabolism*
  • Male
  • Rats
  • Rats, Wistar
  • Receptor, Bradykinin B1 / metabolism
  • Retina / drug effects*
  • Skin / blood supply*
  • Skin / drug effects*
  • Streptozocin / pharmacology

Substances

  • Bradykinin B1 Receptor Antagonists
  • Receptor, Bradykinin B1
  • Streptozocin