Effect of tromboxane synthetase inhibition on platelet function and morphology during ovine pregnancy-induced hypertension

Abstract

Arterial blood pressure, serum fibrin/fibrinogen degratory products, plasma thromboxane B2, in vitro platelet aggregation, and platelet ultrastructure were studied in ten gravid ewes during fast-triggered ovine pregnancy-induced hypertension and subsequent administration of the tromboxane synthetase inhibitors CGS13080 and CGS12970. During the hypertensive period, blood pressurre (p < 0.005) and plasma thromboxane B2 levels (p < 0.005) were significantly altered. Collagen-induced in vitro platelet aggregation lag times increased (p < 0.01), and percent aggregation (p < 0.05), primary (p < 0.01), and secondary (p < 0.005) aggregatory slopes decreased. Collagen also failed to induce aggregation in some ewes. Primary slopes of ADP-induced in vitro platelet aggregation decreased (p < 0.01) during hypertension. Degranulation and open canalicular tubule system swelling were observed in platelets which produced abnormal or no aggregation response. However, these ultrastructural abnormalities did not necessarily correspond to hypertensive periods. Thromboxane synthetase inhibitor administration lowered blood pressure (p < 0.005) and plasma thromboxane B2 levels (p < 0.005). Abnormalities in collagen and ADP-induced platelet aggregation curves were also corrected, and ultrastructural abnormalities were not detected. Marked elevations in plasma thromboxane levels during ovine pregnancy-induced hypertension may have had an 'exhaustive' effect on thrombocytes which was reversed by thromboxane synthetase inhibition.