Plasma- and urine concentrations of nitrite/nitrate and cyclic Guanosinemonophosphate in intrauterine growth restricted and preeclamptic pregnancies.
BACKGROUND
The Nitric Oxide (NO) system plays an important role in the establishment and maintenance of the feto-placental circulation. Research on the pathogenesis of preeclampsia in several studies has established the involvement of the NO-system in preeclampsia and fetal intrauterine growth restriction (IUGR). In the presented study we analyzed the urine and plasma concentrations of nitrite/nitrate, the stable endproducts of NO and its second messenger, cyclic Guanosinemonophosphate (cGMP) in normal, preeclamptic and IUGR pregnancies.


METHODS
In total 76 patients were investigated in a prospective study for repeated determination of plasma and urinary levels of nitrate/nitrite and cGMP: 49 patients with a normal course of pregnancy, 14 patients with fetal IUGR and 13 patients with preeclampsia were included into the study. Plasma and urine Nitrite/Nitrate-concentrations were determined using a Colorimetric Assay (Cayman Inc., USA), concentrations of the second messenger cGMP in plasma and urinary samples were determined with a J(125)-Radio-Immuno-Assay (ibl Inc., Germany). The Stat View Program (Abacus Concepts, Inc., Berkeley, CA, 1992-1998) was used for statistical analysis, a P value <0.05 was considered significant.


RESULTS
Analyzing the data with the Kruskall-Wallis test a significance was reached for Plasma Nitrite/Nitrate (P=0.0236), plasma cGMP (P=0.004) and urinary nitrite/nitrate (P=0.032). No significance was seen for urinary cGMP (P=0.656). Comparing normal and preeclamptic and normal and IUGR pregnancies the following significant differences were seen (Mann-Whitney U test): In preeclamptic pregnancies urine nitrite/nitrate concentration was significantly lower compared to normal pregnancies (P=0.009) No significant difference between normal and preeclamptic pregnancies for plasma nitrite/nitrate (P=0.819) and plasma-cGMP (P=0.072) could be observed. In IUGR pregnancies plasma nitrite/nitrate and the plasma-cGMP concentrations were both significantly lower compared to normal pregnancies (P=0.0077 and 0.0066) in IUGR-pregnancies. No significance was reached when analyzing urine-Nitrite/Nitrate (P=0.7).


CONCLUSIONS
Whereas in preeclampsia a reduced urinary nitrite/nitrate was analyzed, IUGR pregnancies showed reduced plasma nitrite/nitrate and cGMP. A reduced release of NO into the maternal circulation might lead to the presented findings and be involved in the pathogenesis of preeclampsia and fetal IUGR.
Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Ludwig-Maximilians University, 80337 Munich, Germany. Barbara.Schiessl@med.uni-muenchen.de
Barbara
B
Schiessl
Christian
C
Strasburger
Martin
M
Bidlingmaier
Ioannis
I
Mylonas
Udo
U
Jeschke
Franz
F
Kainer
Klaus
K
Friese
D001724:Birth Weight; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D009566:Nitrates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D006152:Cyclic GMP