Human urotensin-II enhances plasma extravasation in specific vascular districts in Wistar rats.
Plasma extravasation (PE) was measured in adult Wistar rats by injecting Evans blue dye (EB) (20 mg kg-1) intravenously in the absence or presence of human urotensin II (U-II) (0.1-10 nmol kg-1). A consistent increase of PE was observed in specific organs (e.g., aorta, from 28.1 +/- 2.4 to 74.6 +/- 3.6 micro g EB g-1 dry tissue; P < 0.001) after an administration of 4.0 nmol kg-1 (a preselected optimal dose) of U-II. The effects of U-II (4.0 nmol kg-1) were compared with those of endothelin-1 (ET-1) (1.0 nmol kg-1). In the thoracic aorta and pancreas, U-II was active, while ET-1 was not. The two agents were equivalent in the heart and kidney, whereas, in the duodenum, ET-1 was more active than U-II. Increases of plasma extravasation induced by U-II, but not by ET-1, were reduced after treatment with [Orn8]U-II (0.3 micromol kg-1). This latter antagonist did not show any significant residual agonistic activity in vivo in the rat. Other specific receptor antagonists for ET-1, such as BQ-123 (endothelin type A (ETA) receptor) and BQ-788 (endothelin type B (ETB) receptor), and for the platelet activating factor (PAF), such as BN50730, failed to modify the action of U-II. The present study is the first report describing the modulator roles of U-II on vascular permeability in specific organs. Moreover, the action of U-II appears specific, since it is independent of the ET-1 and PAF signalling pathways.
Gendron
Gabrielle
G
Institute of Pharmacology, Faculty of Medicine, Universite de Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, Quebec J1K 2R1, Canada.
Simard
Bryan
B
Gobeil
Fernand
F
Sirois
Pierre
P
D'Orléans-Juste
Pedro
P
Regoli
Domenico
D
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D005070:Evans Blue / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000097:blood*; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D014579:Urotensins / Q000378:metabolism / Q000494:pharmacology*
D019332:Endothelin-1; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; D005070:Evans Blue; C029677:urotensin II