Cardiovascular effects of leukotrienes in neonatal piglets. Role in hypoxic pulmonary vasoconstriction?

We investigated the effects of exogenous leukotriene D₄ synthesis inhibitors, and a leukotriene receptor antagonist upon chloralose anesthetized, mechanically ventilated, neonatal piglets with constant left pulmonary blood flow and upon piglets with uncontrolled pulmonary blood flow. Leukotriene D₄ (100-10,000 ng, intravenously) caused dose-dependent increases in peak tracheal pressure, pulmonary vascular resistance, and systemic vascular resistance coupled with dose-dependent decreases in cardiac output and systemic arterial pressure. In a limited number of experiments, cardiovascular responses to exogenous leukotriene C₄ were qualitatively similar but quantitatively less than those to leukotriene D₄. Neither treatment with diethylcarbamazine or the lipoxygenase inhibitor nordihydroguaiaretic acid, nor with the leukotriene receptor antagonist, FPL55712 altered any baseline cardiovascular parameter measured, suggesting the absence of any influence of leukotrienes on resting hemodynamics. Hypoxia or hypoxia combined with mild hypercapnia caused pulmonary vasoconstriction. Neither treatment with diethylcarbamazine or the lipoxygenase inhibitor nordihydroguaiaretic acid, nor with the leukotriene receptor antagonist FPL55712, altered the pulmonary vasoconstrictor response to hypoxia or combined hypoxia/hypercapnia. We conclude that endogenous leukotrienes do not appear to have an influence on resting cardiovascular function, neither do they appear to be necessary for hypoxic pulmonary vasoconstriction in the neonatal piglet, although exogenous leukotrienes are capable of producing cardiovascular effects.