NONCHOLINERGIC MECHANISMS UNDERLYING THE ACUTE LETHAL EFFECTS OF P = S TYPE ORGANOPHOSPHORUS INSECTICIDES IN RATS

Intravenous administration of the lethal dose of diazinon or fenthion, P=S type organophosphates, to urethan anesthetized rats induced bradycardia and transient apnea followed by a decline of blood pressure, and death. We investigated the mechanisms of the lethal action of these organophosphates in rats through measurements of blood pressure, heart rate, and respiratory pattern. We compared their cardiorespiratory effects in the five different conditions under anesthesia; 1) normal (without treatment), 2) artificially ventilated, 3) vagotomized, 4) atropinized, 5) pithed, vagotomized and atropinized. It was found that the administration of 200 mg/kg of fenthion and 100 mg/kg of diazinon, caused sudden bradycardia, transient apnea and gradual decline of blood pressure in the anesthetized normal rat, and the rat died. The rats in other conditions also died except the artificially ventilated rats, in which 400 mg/kg of fenthion was administered to cause hypotension and subsequent death. Hypotension was observed consistently even after the cardiac effect such as bradycardia was eliminated by atropine treatment. In the pithed rats which were further vagotomized and atropinized, these organophosphates also caused hypotension. These results may indicate that hypotension is the main cause of death which resulted from intravenous administration of the P=S types. Hypotension may be caused by peripheral cardiovascular effect of the P=S types, which is unrelated to cholinergic mechanisms.