N-Methylthiobenzamide (NMTB) is a pneumotoxin which causes
pulmonary edema and
hydrothorax in rodents.
Reserpine has been shown to attenuate the pneumotoxicity induced by NMTB. Some of that evidence suggests that the protection afforded by
reserpine occurs independently of its capacity to reduce peripheral
5-hydroxytryptamine (5-HT). We therefore investigated 2 other pharmacologic properties of
reserpine, namely: (1) its capacity to reduce lung
norepinephrine (NE); and (2) its capacity to induce
hypothermia, in order to more fully understand its mechanism of protection. Pretreatment of mice or rats with
6-hydroxydopamine at a dose which reduced lung NE by approximately 80% did not affect the pneumotoxic response to NMTB. Thus a decrease in lung NE probably does not account for
reserpine's protective effect. An investigation of
reserpine's effects on core temperature revealed that mice dosed with a combination of
reserpine + NMTB presented with core temperatures lower than mice treated with either compound alone. Mice placed in a cold environment (2 degrees C) and dosed with NMTB presented with
hypothermia and an attenuated toxic response to NMTB. Thus a
reserpine-
induced hypothermia could be allowing for a reduction of NMTB metabolism and consequent diminution of toxicity. These observations suggest that
reserpine's capacity to protect animals against NMTB-induced
pulmonary edema may in part be due to its capacity to induce
hypothermia.