Evaluation of low-dose endotoxin administration during pregnancy as a model of preeclampsia.
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 microg/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 x kg(-1) x d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 microg/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 microg/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 microg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 microg/kg, and a combination of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity.


CONCLUSIONS
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.
Sakawi
Y
Y
Department of Anesthesiology, University of Alabama at Birmingham, 35233-6810, USA. Yasser.Sakawi@ccc.uab.edu
Tarpey
M
M
Chen
Y F
YF
Calhoun
D A
DA
Connor
M G
MG
Chestnut
D H
DH
Parks
D A
DA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D004731:Endotoxins / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000652:urine; D011225:Pre-Eclampsia / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D019331:NG-Nitroarginine Methyl Ester