Effect of reserpine on N-methylthiobenzamide-induced pulmonary edema: role of lung norepinephrine and hypothermia.
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.
Gibbs
L S
LS
Department of Pharmacology and Toxicology, University of Kansas, School of Pharmacy, Lawrence 66045-2500.
Traiger
G J
GJ
D000577:Amides / Q000633:toxicity*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003080:Cold Temperature; D006892:Hydroxydopamines / Q000494:pharmacology; D007036:Hypothermia, Induced; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D016627:Oxidopamine; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000517:prevention & control; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013854:Thioamides / Q000378:metabolism / Q000633:toxicity*
D000577:Amides; D006892:Hydroxydopamines; D013854:Thioamides; D012701:Serotonin; C046391:N-methylthiobenzamide; D012110:Reserpine; D016627:Oxidopamine; D009638:Norepinephrine