Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced vascular permeability in type 1 diabetic mice.
The morbidity and mortality associated with type 1 diabetes are essentially related to the micro- and macrovascular complications that develop over time and lead to several diabetic complications, including hypertension, atherosclerosis, and retinopathy, as well as coronary and renal failure. Normally absent in physiological conditions, the bradykinin B1 receptor (BKB1-R) was recently found to be overexpressed in pathological conditions, including type 1 diabetes. In the present study, we evaluated the effect of the new BKB1-R antagonist, R-954 (Ac-Orn-[Oic2, alpha-MePhe5, D-betaNal7, Ile8]desArg9-bradykinin, on the increase in vascular permeability in streptozotocin (STZ)-diabetic mice. The capillary permeability to albumin was measured by quantifying the extravasation of albumin-bound Evans blue dye in selected target tissues (liver, pancreas, duodenum, ileum, spleen, heart, kidney, stomach, skin, muscle, and thyroid gland). Acute single administration of R-954 (300 microg/kg, i.v.) to type 1 diabetic mice 4 weeks after STZ significantly inhibited the enhanced vascular permeability in most tissues. These data provide further experimental evidence for the implication of BKB1-R in the enhanced vascular permeability associated with type 1 diabetes.
Simard
Bryan
B
Institute of Pharmacology of Sherbrooke, School of Medicine, University of Sherbrooke, Sherbrooke, PQ J1H 5N4, Canada.
Gabra
Bichoy H
BH
Sirois
Pierre
P
D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000502:physiology
C476306:Ac-Orn-(Oic2, alpha-MePhe5, D-betaNal7, Ile8)desArg9-bradykinin; D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D001920:Bradykinin