Release of thromboxane A2 by low-dose almitrine in the hypoxic dog

Potentiation of hypoxic pulmonary vasoconstriction by a low dose of almitrine bismesylate (1 microgram.kg-1.min-1) was evaluated in terms of blood chemical mediator concentrations. Time course changes in the blood concentrations of adrenaline, noradrenaline, serotonin, histamine, thromboxane TXB2 and 6-keto-PGF1 alpha were monitored after administration of almitrine bismesylate for 15 min at 1 microgram.kg-1.min-1) in hypoxic and normoxic beagles. The low almitrine dose significantly increased TXB2 levels in hypoxic beagles, but the levels remained virtually unchanged in the normoxic animals with almitrine bismesylate and in the hypoxic animals with solvent. TXB2 levels did not increase when the almitrine infusion was increased to 5 micrograms.kg-1.min-1 for 15 min in hypoxic conditions. These findings suggest that almitrine is involved in arachidonic acid metabolism at a low rate of infusion and that thromboxane release from hypoxic areas of the lung may cause local vasoconstriction.