Local haemorrhage induced by Bothrops jararaca venom: relationship to neurogenic inflammation

WE investigated morphological alterations Induced by s.c. injection of 2.5 mu g of Bothrops jararaca venom in rats. Intense disorganisation of collage n fibres was observed 1 min after the venom injection, particularly at regi ons near vessels and nerves. Mast cells were degranulated, and erythrocytes were seen leaving venules throughout the endothelial junctions, At this ti me, damaged endothelial cells were not observed. In rats envenomed as above , but immediately after cardiorespiratory failure induced by deep ether ana esthesia, alterations in the connective tissue structures, as previously de scribed, were not observed, The mediation of this haemorrhage was investiga ted by injecting the venom into the foot pad of mice and compared to the me diation of oedema, Local haemorrhage was significantly reduced in mice pre- treated with capsaicin or guanethidine or submitted to a surgical section o f sciatic and saphenous nerves. In these animals, oedema was not affected. Groups treated with methysergide or morphine showed both haemorrhage and oe dema significantly reduced. Indomethacin or dexamethasone pre-treatments si gnificantly reduced the oedema, but not the haemorrhage. Moreover, In anima ls treated with promethazine or mepyramine, oedema and haemorrhage were not affected. These data suggest that local haemorrhage Induced by Bothrops ja raraca venom is partially controlled by serotonin and neurohumoral mediator s. Furthermore, results indicate that haemorrhage and oedema are mediated b y different pharmacological systems.