title: Protective effects of ethynylestradiol on the hemodynamic changes induced by lipopolysaccharide in anesthetized rats.
abstract: Estrogen pretreatment has been reported to protect rats from death induced by endotoxin. We investigated the effects of posttreatment with a synthetic estrogen, ethynylestradiol, on arterial pressure and hemodynamics in thiobutabarbitone-anesthetized rats challenged with Escherichia coli lipopolysaccharide. Rats were i.v. injected with lipopolysaccharide (1 mg/kg) followed by vehicle or a single dose of ethynylestradiol (0.25, 0.5, or 1 mg/kg) 1 h later. Another group (time-matched control) was given the vehicle. In the time-control group, there was a slight decrease in mean arterial pressure (-10 +/- 3 mm Hg) but no significant changes in cardiac output, total peripheral resistance, or heart rate over the 6-h study period. Lipopolysaccharide progressively reduced mean arterial pressure and cardiac output (-27 +/- 8 mm Hg and -52 +/- 6 ml/min, after 6 h) and increased total peripheral resistance and heart rate (+0.33 +/- 0.10 mm Hg/min/ml and +21 +/- 13 beats/min, after 6 h). None of the time-control rats died, but 36% of the rats treated with lipopolysaccharide died between 3 and 6 h after endotoxin challenge. Ethynylestradiol, at 0.25 and 0.5 completely, and at 1 mg/kg partially, restored mean arterial pressure and cardiac output at 6 h after injection of lipopolysaccharide. Ethynylestradiol at 0.5 and 1 mg/kg, but not 0.25 mg/kg, completely reversed the increase in total peripheral resistance at 6 h after injection of lipopolysaccharide. Mortality was 14% in each of the three groups of rats given ethynylestradiol 1 h after lipopolysaccharide. Therefore posttreatment with ethynylestradiol attenuated hemodynamic changes in endotoxic shock.
authors.affiliation: Department of Pharmacology & Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Palacios
authors.forename: C C
authors.initials: CC
authors.lastname: Pang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004926:Escherichia coli; D045166:Estradiol Congeners / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D045166:Estradiol Congeners; D008070:Lipopolysaccharides; D004997:Ethinyl Estradiol