Evaluation of low-dose endotoxin administration during pregnancy as a model of preeclampsia

Background: Recent evidence implicates nitric oxide((NO)-N-.) in the pathog enesis of preeclampsia, The authors tested the hypothesis that administrati on of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that (NO)-N-. and (NO)-N-.-derived species play a role in tha t animal model. Methods: Endotoxin was infused at doses of 1, 2 and 10 mug/kg over 1 h to r ats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinar y and plasma nitrite plus nitrate(NO2- + NO;) concentrations, and platelet count were measured before and after the endotoxin infusion. In another gro up of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine me thyl ester (L-NAME) was administered in drinking water at a dose of 3 mg.kg (-1).d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 mug/kg on day 14 of pregnancy. Kidneys and uteroplacental units were exami ned histologically and analyzed immunohistochemically for 3-nitrotyrosine. Results: Endotoxin administration at doses of 2 and 10 mug/kg caused protei nuria and thrombocytopenia in pregnant rats, but did not result in hyperten sion. Urinary NO2- + NO3- concentration, reflective of tissue (NO)-N-. prod uction rates, was significantly elevated in pregnant rats that received end otoxin at 10 mug/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 mug/kg, and a combinatio n of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity. Conclusion: Nitric oxide either directly or through secondary species plays a significant role in the biochemical and physiologic changes that occur i n a rodent model of endotoxin-induced injury.