Sub-acute effects of the 17beta-aminoestrogen pentolame and estradiol on hemostasis in the rat.

Abstract

This work describes the sub-acute treatment of male Wistar rats with estradiol (E2) and the 17beta-aminoestrogen pentolame (AEP) on the hemostatic screening tests: blood clotting time (BCT), prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT) and fibrinogen concentrations (FIB). Animals received five consecutive subcutaneous (s.c.) doses of E2 (1 and 10 mg/kg) and AEP (5, 10 and 20 mg/kg) and the course of blood clotting times (BTC) was followed 24, 48, 72 and 96 hr after finishing treatment. Five injections of equivalent doses (0.1, 1, 10, 100 or 1000 microg/kg) of both steroids were performed. In all experiments a control group (propylenglycol 1 ml/kg) was included. Individual blood samples were obtained (under anesthesia) from the iliac artery and PT, aPTT, TT, and FIB were determined according to previous reported techniques. Forty-eight hr after treatment, E2 decreased BCT (10%) while AEP increased BCT 87% in a dose dependent manner. Only E2 significantly decreased FIB concentration (p<0.5; 25%) while AEP induced a dose dependent increase in FIB from 18 to 88%, (p < 0.05). AEP produced biphasic responses on aPTT (+24 % and -15%; p<0.05) and decreased TT from 11 to 14%, (p<0.01). AEP aPTT vs. FIB showed a r2=-0.99, (p < 0.05). Pentolame showed disparate effects compared with E2 on the blood clotting parameters and exerts its most important effects on the common coagulation pathway.