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 F1 alpha 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 less than 0.03), and returned to normal after U-63,557A. Left uterine artery blood flow increased after U-63,557A (p less than 0.03). Creatinine clearance decreased during hypertension (p less than 0.03) and increased after U-63,557A. Urine protein increased during hypertension (p less than 0.03) and decreased after treatment. Platelet count dropped during hypertension (p less than 0.03) and was elevated after treatment. Collagen lag phase decreased during hypertension (p less than 0.03) and increased after treatment. After U-63,557A, 6-ketoprostaglandin F1 alpha levels were higher (p less than 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.