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 μg/site) dose-dependently increase the vascular permeability in rats, an effect unchanged by indomethacin (5 mg/kg, i.p.), atropine (1 mg/kg, i.p.), HOE-140 (2 mg/kg, s.c.) or SR140333 (0.3 mg/kg, i.p.), but fully avoided by promethazine (15 mg/kg, i.p.), methysergide (2 mg/kg, i.p.) and compound 48/80 (3 mg/kg/day for 3 days). Addition of cumulative concentrations of LIV (0.1–5 μg) in phenylephrine-contracted aortic rings resulted in a partial (∼40%) and endothelium-dependent relaxation, inhibited by the nitric oxide synthase inhibitors l-NAME (10 μM) and l-NMMA (1 mM), and the guanylate cyclase inhibitors methylene blue (100 μM) and ODQ (10 μM). LIV-induced relaxation was abolished by compound 48/80 (10 μM) and pyrilamine (a selective histamine H1 receptor antagonist; 100 μM), but not by atropine (1 μM) and indomethacin (10 μM). 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 serotonine.