thromboxane-a2 and piriprost

Intravenous infusion of free fatty acid (FFA) 20 mg.kg-1.min-1 produces pulmonary edema, hypoxemia, hyperventilation and increase in the alveolar surfactant content in rabbits in less than 15 min. We tried to study the role of leukotrienes (LT) and the effects of PGI2 in pulmonary response to FFA. We used Piriprost an inhibitor of LT synthesis or Epoprostenol (Prostacyclin: PGI2) in 4 series of rabbits treated with FFA or its vehicle. Piriprost given as an aerosol (0.1% W/W in THAM) scarcely modified the morphofunctional changes induced by FFA. The only pulmonary effect prevented by Piriprost was the increase in surfactant content (disaturated phosphatidylcholine: DSPC) in broncho-alveolar lavage gluid (BAL). PGI2 administered in a dose of 0.1 micrograms.kg-1.min-1 5 minutes prior to a 15 min infusion of FFA was also unable to prevent most of the effects of FFA on the lung. Only the increase in DSPC in BAL was prevented by PGI2. Some animals received a smaller dose of FFA, because they died earlier. Piriprost, as well as PGI2, shortened the survival time of rabbits treated with FFA. This decrease in the survival rate of animals treated with FFA could account for the lack of increase in DSPC post-FFA. Since other morphofunctional changes induced by FFA were scarcely modified by both Piriprost or PGI2, our results suggest that it is unlikely that either leukotrienes on PGI2 may have a significant effect on pulmonary disturbances induced by FFA.

Topics: Animals; Epoprostenol; Fatty Acids, Nonesterified; Hemodynamics; Infusions, Intravenous; Leukotrienes; Lung; Male; Rabbits; Thromboxane A2

Leukotrienes C4 and D4 and thromboxane A2 are potent vasoconstrictors that may mediate pulmonary vasoconstriction in many clinical situations. There is a complex interaction among leukotrienes and thromboxane A2, because inhibition of thromboxane synthesis prevents some of the hemodynamic effects of exogenous leukotrienes. Similarly, if leukotrienes mediate thromboxane A2-induced pulmonary vasoconstriction, then leukotriene antagonists should attenuate the effects of a thromboxane A2-mimetic such as U46619. First, dose response curves for the hemodynamic effects of U46619 were performed on seven spontaneously breathing newborn lambs. Then a putative leukotriene receptor antagonist, FPL57231, 1 mg/kg/min, or a putative leukotriene synthesis antagonist, U60257, 30 mg/kg, was given before infusing U46619 (1 microgram/kg/min). U46619 caused significant dose-dependent increases in pulmonary and systemic arterial pressures (p less than 0.05) and significant dose-dependent decreases in cardiac output and heart rate (p less than 0.05). A 1 microgram/kg/min infusion of U46619 increased pulmonary arterial pressure by 155.4% +/- 8.9 and systemic arterial pressure by 8.9% +/- 7.7 and decreased cardiac output by 19.7% +/- 12.2 and heart rate by 9.9% +/- 10.6. FPL57231 attenuated the effects of U46619. U60257 had similar effects. Therefore, the hemodynamic effects of thromboxane A2, an important mediator of the pulmonary vasoconstriction produced, for example, by group B streptococci and Escherichia coli, may be mediated by the secondary production of leukotrienes.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Animals, Newborn; Blood Pressure; Cardiac Output; Chromones; Epoprostenol; Hypertension, Pulmonary; Lipoxygenase Inhibitors; Prostaglandin Endoperoxides, Synthetic; Sheep; SRS-A; Thromboxane A2