Beneficial effects of U-63 557A a thromboxane synthetase inhibitor, in an ovine model of pregnancy-induced hypertension

Pregnancy-induced hypertension was induced in five ewes (gestational day 135; term 150 days) by 72 hours of food deprivation. Maternal arterial pressure, uterine blood flow, platelet function, renal function, and plasma levels of 6-ketoprostaglandin F_1α and thromboxane B₂ were measured before and during hypertension and after three intravenous injections of U-63,557A; sodium 5-(3′-pyridinylmethyl) benzofuran-2-carboxylate, monohydrate (30 mg/kg every 8 hours). Blood pressure increased (p < 0.03), and returned to normal after U-63,557A. Left uterine artery blood flow increased after U-63,557A (p < 0.03). Creatinine clearance decreased during hypertension (p < 0.03) and increased after U-63,557A. Urine protein increased during hypertension (p < 0.03) and decreased after treatment. Platelet count dropped during hypertension (p < 0.03) and was elevated after treatment. Collagen lag phase decreased during hypertension (p < 0.03) and increased after treatment. After U-63,557A, 6-ketoprostagland in F_1α levels were higher (p < 0.04) than baseline or hypertensive values. Administration of a thromboxane synthetase inhibitor caused resolution of hemodynamic, renal, and coagulation dysfunctions that occurred in ovine pregnancy-induced hypertension.