[Pharmacological studies on the mechanisms of asebotoxin III-induced centrogenic pulmonary hemorrhagic edema in guinea pigs].

Asebotoxin III (ATX-III), a diterpenoid isolated from the leaves of Asebi, Pieris japonica, was found to produce hemorrhage into the lungs when the toxin in a dose of 2-8 micrograms was injected into the lateral ventricle of guinea pigs under urethane anesthesia (0.8 g/kg, i.p.). The occurrence of the lung hemorrhage was associated with a hypertensive response which was two times higher than the control level. The hemorrhage first occurred at a time when systemic blood pressure reached its highest level. This was verified by X-ray examination on the chest of the guinea pig. In contrast to the hemorrhage into the lungs, the other organs in the abdominal cavity were found to be rather ischemic in the autopsy cases. Death due to hemorrhage into the lungs was effectively prevented by pretreating the guinea pigs with phentolamine mesylate (1 mg/kg, i.v.) and 6-hydroxydopamine hydrobromide (40 mg/kg, i.p.). Time before death was significantly prolonged by treating the animals with reserpine (5 mg/kg, i.m.), chlorpromazine hydrochloride (10 mg/kg, i.v.), guanethidine sulfate (20 mg/kg, i.v.), and hexamethonium bromide (5 mg/kg, i.v.), though death from the lung hemorrhage was not completely blocked. The hemorrhage was aggravated by pretreatment with atropine sulfate (5 mg/kg, i.v.). EEG recordings from the hypothalamus of guinea pigs with ATX-III injection showed an exciting pattern of waves of high frequency and spike discharge. On the mechanisms for the lung hemorrhage induced by ATX-III, we concluded that the toxin produced depolarization of some neurones in the hypothalamus, thereby provoking massive sympathetic discharge for producing severe pulmonary hypertension and hemorrhage.