Influence of thromboxane A₂ receptor antagonism on pulmonary vasoconstrictor responses

Thromboxane A₂ (TxA₂) is an arachidonic acid metabolite which causes severe pulmonary vasoconstriction (PV) and may mediate the PV produced by platelet-activating factor (PAF-acether) and leukotriene D₄ (LTD₄). To determine the role of TxA₂ receptors on PAF-acether, LTD₄, and hypoxia-induced PV, we administered PAF-acether 0.1 μmol/kg, the TxA₂ analog U-46619 0.2 μg/kg/min, LTD4 3.0 Mg/kg, or acute hypoxia (Fio2 = 0.12 for 3 min) before and during the infusion of the selective TxA₂ receptor blocker SQ 29 548 50 μ/xg/kg/min or vehicle into 27 open-chest, anesthetized newborn piglets, measuring pulmonary and systemic arterial pressures, cardiac index, and right and left ventricular pressures and dimensions. Mean pulmonary arterial pressure rose and cardiac index fell in response to PAF-acether (14 ± 1 to 32 ± 2 mm Hg and 91 ± 5 to 15 ± 5 μL/kg/min, both p < 0.01), U-46619 (11 ± 1 to 28 ± 2 mm Hg and 93 ± 10 to 36 ± 9 μL/kg/min, both p < 0.01), and LTD4 (13 ± 3 to 22 ± 2 mm Hg and 85 ± 12 to 29 ± 9 μL/kg/min, both p < 0.05). Acute hypoxia increased PAP (12 ± 1 to 26 ± 2 mm Hg, p < 0.01) but did not alter cardiac index. Infusion of SQ 29 548 prevented PAF-acether and U-46619-induced increases in pulmonary arterial pressure (13 ± 1 to 14 ± 1 mm Hg and 12±1 to l2±1 mm Hg) and decreases in cardiac index (70 ± 4 to 70 ± 3 μL/kg/min and 94 ± 14 to 92 ± 12 μL/kg/min) but failed to alter the response to LTD4 or hypoxia. Vehicle had no effect. We conclude that TxA₂ receptors are not involved in LTD4 or hypoxia-induced PV but play an important role in the PV produced by PAF-acether and U-46619.