Inhibition of endotoxin-induced pulmonary vasoconstriction in dogs by alpha-methyl dopa

Abstract

The demonstration in a previous study of the effectiveness of an antihistaminic drug in blocking some of the systemic but not the pulmonary vascular effects of endotoxin led to the study of the effect of an inhibitor of serotonin synthesis, alpha-methyl 3,4-dihydroxyphenylalanine (α-m dopa). One group of seven dogs was pretreated with a single dose of 250 mg, and a second group of six animals with three doses of 250 mg, each given at 10-min intervals. Results in these two groups were compared with those in six control animals. Purified E. coli endotoxin, 1 mg/kg, was administered intravenously in all 19 experiments. Intravenous administration of α-m dopa alone had no effect on measured physiologic parameters. Compared with the endotoxin response in control animals, pretreatment with either dose level appeared to have no effect on the magnitude or duration of systemic arterial hypotension, portal venous hypertension, or drop in cardiac output. However, pretreatment with 250-mg and 750-mg doses was associated with significant reduction and abolition, respectively, of pulmonary arterial hypertension. The results are consistent with the interpretation that the pulmonary vasoconstrictive response to endotoxin is mediated through the release of serotonin and that α-m dopa blocks this response by interfering with the synthesis of this intermediary.