Bradley L M, Stambouly J J, Czaja J F, Goldstein R E
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Pediatr Res. 1989 Sep;26(3):175-9. doi: 10.1203/00006450-198909000-00002.
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 nmol/kg, the TxA2 analog U-46619 0.2 micrograms/kg/min, LTD4 3.0 micrograms/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 micrograms/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 mL/kg/min, both p less than 0.01), U-46619 (11 +/- 1 to 28 +/- 2 mm Hg and 93 +/- 10 to 36 +/- 9 mL/kg/min, both p less than 0.01), and LTD4 (13 +/- 3 to 22 +/- 2 mm Hg and 85 +/- 12 to 29 +/- 9 mL/kg/min, both p less than 0.05). Acute hypoxia increased PAP (12 +/- 1 to 26 +/- 2 mm Hg, p less than 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 12 +/- 1 mm Hg) and decreases in cardiac index (70 +/- 4 to 70 +/- 3 mL/kg/min and 94 +/- 14 to 92 +/- 12 mL/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.
血栓素A2（TxA2）是一种花生四烯酸代谢产物，可引起严重的肺血管收缩（PV），并可能介导由血小板活化因子（PAF-乙酰醚）和白三烯D4（LTD4）产生的肺血管收缩。为了确定TxA2受体在PAF-乙酰醚、LTD4和缺氧诱导的肺血管收缩中的作用，我们在向27只开胸、麻醉的新生仔猪输注选择性TxA2受体阻滞剂SQ 29,548 50微克/千克/分钟或溶媒之前及期间，给予PAF-乙酰醚0.1纳摩尔/千克、TxA2类似物U-46619 0.2微克/千克/分钟、LTD4 3.0微克/千克或急性缺氧（吸入氧分数=0.12，持续3分钟），同时测量肺动脉和体动脉压力、心脏指数以及左右心室压力和尺寸。PAF-乙酰醚（分别从14±1至32±2毫米汞柱和91±5至15±5毫升/千克/分钟，两者p均小于0.01）、U-46619（分别从11±1至28±2毫米汞柱和93±10至36±9毫升/千克/分钟，两者p均小于0.01）和LTD4（分别从13±3至22±2毫米汞柱和85±12至29±9毫升/千克/分钟，两者p均小于0.05）可使平均肺动脉压升高，心脏指数降低。急性缺氧可使肺动脉压升高（从12±1至26±2毫米汞柱，p小于0.01），但不改变心脏指数。输注SQ 29,548可预防PAF-乙酰醚和U-46619诱导的肺动脉压升高（分别从13±1至14±1毫米汞柱和12±1至12±1毫米汞柱）以及心脏指数降低（分别从70±4至70±3毫升/千克/分钟和94±14至92±12毫升/千克/分钟），但未能改变对LTD4或缺氧的反应。溶媒无作用。我们得出结论，TxA2受体不参与LTD4或缺氧诱导的肺血管收缩，但在PAF-乙酰醚和U-46619产生的肺血管收缩中起重要作用。
