PROTECTIVE EFFECTS OF ETHYNYLESTRADIOL ON THE HEMODYNAMIC-CHANGES INDUCED BY LIPOPOLYSACCHARIDE IN ANESTHETIZED RATS

Estrogen pretreatment has been reported to protect rats from death ind uced by endotoxin. We investigated the effects of posttreatment with a synthetic estrogen, ethynylestradiol, on arterial pressure and hemody namics in thiobutabarbitone-anesthetized rats challenged with Escheric hia coli lipopolysaccharide. Rats were i.v. injected with lipopolysacc haride (1 mg/kg) followed by vehicle or a single dose of ethynylestrad iol (0.25, 0.5, or 1 mg/kg) 1 h later. Another group (time-matched con trol) was given the vehicle. In the time-control group, there was a sl ight decrease in mean arterial pressure (-10 +/- 3 mm Hg) but no signi ficant changes in cardiac output, total peripheral resistance, or hear t late over the 6-h study period. Lipopolysaccharide progressively red uced mean arterial pressure and cardiac output (-27 +/- 8 mm Hg and -5 2 +/- 6 ml/min, after 6 h) and increased total peripheral resistance a nd heart rate (+0.33 +/- 0.10 mm Hg/min/ml and +21 +/- 13 beats/min, a fter 6 h). None of the time-control rats died, but 36% of the rats tre ated with lipopolysaccharide died between 3 and 6 h after endotoxin ch allenge. Ethynylestradiol, at 0.25 and 0.5 completely, and at 1 mg/kg partially, restored mean arterial pressure and cardiac output at 6 h a fter injection of lipopolysaccharide. Ethynylestradiol at 0.5 and 1 mg /kg, but not 0.25 mg/kg, completely reversed the increase in total per ipheral resistance at 6 h after injection of lipopolysaccharide. Morta lity was 14% in each of the three groups of rats given ethynylestradio l 1 h after lipopolysaccharide. Therefore posttreatment with ethynyles tradiol attenuated hemodynamic changes in endotoxic shock.