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

Academic Article

Abstract

  • Background: Recent evidence implicates nitric oxide (· NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that · NO and · NO-derived species play a role in that animal model. Methods: Endotoxin was infused at doses of 1, 2 and 10 μg/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2/- + NO3/-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine methyl 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 μg/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine. Results: Endotoxin administration at doses of 2 and 10 μg/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2/- + NO3/- concentration, reflective of tissue · NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 μg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 μg/kg, and a combination 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 in a rodent model of endotoxin-induced injury.
  • Digital Object Identifier (doi)

    Author List

  • Sakawi Y; Tarpey M; Chen YF; Calhoun DA; Connor MG; Chestnut DH; Parks DA
  • Start Page

  • 1446
  • End Page

  • 1455
  • Volume

  • 93
  • Issue

  • 6