Vascular permeability and vasodilation induced by the Loxosceles intermedia venom in rats: involvement of mast cell degranulation, histamine and 5-HT receptors.
The mechanisms involved in both local and systemic effects of Loxosceles intermedia (brown spider) venom (LIV) are still poorly understood. We show using rats treated with Evans blue dye (50 mg/kg, i.v.) that small doses of the LIV (0.1, 0.3, 1 and 3 microg/site) dose-dependently increase the vascular permeability in rats, an effect unchanged by indomethacin (5mg/kg, i.p.), atropine (1mg/kg, i.p.), HOE-140 (2mg/kg, s.c.) or SR140333 (0.3mg/kg, i.p.), but fully avoided by promethazine (15 mg/kg, i.p.), methysergide (2mg/kg, i.p.) and compound 48/80 (3mg/kg/day for 3 days). Addition of cumulative concentrations of LIV (0.1-5 microg) in phenylephrine-contracted aortic rings resulted in a partial ( approximately 40%) and endothelium-dependent relaxation, inhibited by the nitric oxide synthase inhibitors L-NAME (10 microM) and L-NMMA (1mM), and the guanylate cyclase inhibitors methylene blue (100 microM) and ODQ (10 microM). LIV-induced relaxation was abolished by compound 48/80 (10 microM) and pyrilamine (a selective histamine H1 receptor antagonist; 100 microM), but not by atropine (1 microM) and indomethacin (10 microM). Our results disclose that LIV increases vascular permeability and induces vascular relaxation. These effects occur due to its ability to degranulate mast cells and release mediators such as histamine and serotonin.
Department of Pharmacology, Centro de Ciências Biológicas, Universidade Federal of Paraná, Curitiba, PR, Brazil.
Yanna D
YD
Rattmann
Carlos R
CR
Pereira
Yara
Y
Cury
Waldemiro
W
Gremski
M Consuelo A
MC
Marques
J Eduardo
JE
da Silva-Santos
D000818:Animals; D001011:Aorta / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects*; D006632:Histamine / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013111:Spider Venoms / Q000378:metabolism / Q000633:toxicity*; D013112:Spiders / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D011985:Receptors, Serotonin; D013111:Spider Venoms; C055161:loxosceles venom; D012701:Serotonin; D006632:Histamine; D010727:Phosphoric Diester Hydrolases