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Increases in serum nitrite and nitrate of a few-fold adversely affect the outcome of pregnancy in rats.

Abstract
The objective of this study was to evaluate serum nitrite and nitrate (nitrite/nitrate) concentrations that affect adversely pregnancy outcome. Pregnant rats, from day 2 to day 8 of pregnancy, were daily given subcutaneously several doses (5, 10, and 30 mg/rat) of diethylenetriamine-nitric oxide (DETA/NO). Serum nitrite/nitrate concentrations were measured using an HPLC system. Serum nitrite/nitrate concentrations increased dose-dependently with DETA/NO. Effects of DETA/NO on pregnancy outcome were assessed on day 14 of pregnancy. In rats given 5 mg DETA/NO, there was a significant increase in serum nitrite/nitrate concentrations (49.2 vs 24.6 micromol/l, P<0.001), and both placental weight and fetal weight decreased compared to control rats. Macroscopic bleeding in placenta was frequently observed in rats given DETA/NO. We further studied effects of DETA/NO on cultured trophoblastic BeWo cells. DETA/NO added to the culture medium increased nitrite/nitrate concentrations in the medium in a dose-dependent manner. Nitrite/nitrate concentrations in the medium over four times the concentration of control decreased progesterone in the medium at 24 h after the application of DETA/NO. The hormonal secretion was not affected by DETA only. This study shows for the first time nitrite/nitrate concentrations affecting adversely pregnancy outcome and function of the trophoblastic cells.
AuthorsTsuneo Inoue, Muneshige Kaibara, Yasuko Sakurai-Yamashita, Masahiro Kawano, Tadayuki Ishimaru, Kohtaro Taniyama
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 95 Issue 2 Pg. 228-33 (Jun 2004) ISSN: 1347-8613 [Print] Japan
PMID15215647 (Publication Type: Journal Article)
Chemical References
  • Chorionic Gonadotropin
  • Culture Media
  • Hormones
  • Nitrates
  • Nitric Oxide Donors
  • Nitrites
  • Polyamines
  • diethylenetriamine
  • Nitric Oxide
  • Progesterone
Topics
  • Animals
  • Cell Line
  • Cell Proliferation (drug effects)
  • Chorionic Gonadotropin (metabolism)
  • Culture Media
  • Female
  • Fetal Weight (drug effects)
  • Half-Life
  • Hormones (metabolism)
  • Humans
  • Nitrates (blood)
  • Nitric Oxide (metabolism)
  • Nitric Oxide Donors (pharmacology)
  • Nitrites (blood)
  • Placenta (drug effects)
  • Placentation
  • Polyamines (pharmacology)
  • Pregnancy
  • Pregnancy Outcome
  • Progesterone (metabolism)
  • Rats
  • Rats, Wistar
  • Trophoblasts (drug effects)

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