Abstract
ABSTRACT: 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 μg/kg/min). U46619 caused significant dose-dependent increases in pulmonary and systemic arterial pressures (p < 0.05) and significant dose-dependent decreases in cardiac output and heart rate (p < 0.05). A 1 μg/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.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Soifer, S., Schreiber, M. & Heymann, M. Leukotriene Antagonists Attenuate Thromboxane-Inducible Pulmonary Hypertension. Pediatr Res 26, 83–87 (1989). https://doi.org/10.1203/00006450-198908000-00001
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-198908000-00001