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.