Evaluation of nitric oxide as a mediator of severe preeclampsia

Abstract

Objective: Our purpose was to determine whether a reduction in nitric oxide synthesis occurs in women with severe preeclampsia as a consequence of soluble serum factors.

Study design: Circulating nitrate and nitrite levels were compared between women who met standard clinical criteria for severe preeclampsia (n = 21) and maternal or gestational age-matched, normotensive, primagravid control subjects (n = 21). End-products of nitric oxide synthesis were measured from venous blood samples using nitrate reduction and chemiluminescence. To detect in vitro suppression of nitric oxide synthesis, human umbilical vein endothelial cell monolayers were grown to confluence and exposed to culture media containing 20% severe preeclamptic or control sera. Nitrate and nitrite production were compared in duplicate monolayers for each experimental condition, expressed as means +/- SEM in picomoles per 10(6) cells. Data were compared by Student's t or Mann-Whitney U tests, when appropriate, along with Spearman correlations for comparisons of laboratory and clinical data.

Results: Circulating nitrate and nitrite levels were similar in normotensive and preeclamptic cohorts (976 +/- 88 vs 1009 +/- 41 pmol/ml, respectively; p = 0.22), and no correlations between blood pressure and nitric oxide metabolite levels were observed for the control or severely preeclamptic subsets. Similar patterns of in vitro endothelial nitrite production were observed after 1-, 12-, and 24-hour incubations with 20% control or preeclamptic sera.

Conclusions: Circulating nitrate and nitrite levels are not reduced in patients with severe preeclampsia compared with normotensive controls, and sera from these women do not suppress endothelial cell nitric oxide synthesis in vitro.