Characterisation of some pharmacological effects of the venom from Vipera lebetina.

Vipera lebetina is one of the most venomous snakes on the Iran plateau. Serious clinical problems such as edema, hemorrhage and tissue necrosis are observed in humans following V. lebetina envenomating. However, little information on the pharmacological properties of the venom is available. To determine haemodynamic actions of the venom of V. lebetina, the changes in the mean arterial blood pressure of anaesthetised rats following the administration of the venom were recorded. Venom (1 mg/kg, i.v.) produced rapid cardiovascular collapse, while 0.3 mg/kg (i.v.) caused only a small transient decrease in mean arterial blood pressure. Effects of the venom on perfusion pressure in the isolated rat mesenteric bed, and on contractions of the isolated rat right atrium and the isolated guinea-pig ileum, were also studied. Exposure of the isolated rat right atrium to venom (0.1-1 mg/ml) caused a transient increase followed by a sustained reduction in the amplitude and frequency of spontaneous contractions. The transient positive inotropic and chronotropic effects were abolished when the preparation was preincubated with propranolol, but not with tolazoline. N(G)-nitro-l-arginine methyl ester pretreatment attenuated the vascular hyporeactivity to phenylephrine induced by the venom in the isolated rat mesenteric vascular bed. This suggests that nitric oxide (NO) or NO-like compounds may be present in the venom and involved in its hypotensive effect. The venom (0.3-1 mg/ml) caused concentration-dependant blockade of isolated guinea-pig ileum contractions induced by electrical field stimulation, acetylcholine or KCl. This inhibitory effect of the venom was significantly reduced by prior incubation of the venom with manoalide (1 microM) indicating involvement of a phospholipase A(2) component. Further, investigation is required to identify specific toxins responsible for the above pharmacological effects.