title: Thromboxane is not responsible for the high pulmonary vascular resistance in fetal lambs.
abstract: The factors responsible for the high pulmonary vascular resistance in the fetus are not well known. Thromboxane (TX) A2 is a potent pulmonary vasoconstrictor. To determine whether TXA2 may play a role in fetal pulmonary vasoconstriction, we infused the specific TX synthetase inhibitor U63,557A into eight chronically instrumented fetal lambs (134-137 days gestational age, full term 145 days) and measured pulmonary blood flow, pulmonary and systemic arterial pressure, and heart rate. U63,557A (3 mg/kg as a bolus then 3 micrograms/kg/min for 120 min infused in the main pulmonary artery) did not change pulmonary blood flow, pulmonary mean arterial pressure, and pulmonary vascular resistance during the infusion and during 2 h following the end of the infusion. During the infusion, TXB2 arterial plasma concentrations decreased from 106.1 +/- 17.5 to 8.7 +/- 2.9 pg/ml. In three of the fetal lambs, immediately after the 2-h infusion of U63,557A, we infused the leukotriene end-organ antagonist FPL 57231 into the main pulmonary artery (1 mg/kg/min for 60 min). TXA2 synthesis inhibition did not prevent the pulmonary vasodilation induced by FPL 57231. Pulmonary blood flow increased from 64.8 +/- 24.4 to 669.5 +/- 65.6 ml/min/100 g lung tissue during the FPL 57231 infusion. We conclude that TXA2 does not play a role in the maintenance of elevated fetal pulmonary vascular tone, either directly or as a mediator of leukotriene action.
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000502:physiology*; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects; D013189:SRS-A / Q000037:antagonists & inhibitors; D012756:Sheep; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D001572:Benzofurans; D002867:Chromones; D013189:SRS-A; D013928:Thromboxane A2; C034338:FPL 57231; D013930:Thromboxane-A Synthase; C039936:furegrelate