The role of nitric oxide in the pathogenesis of preeclampsia.
OBJECTIVE
Nitric oxide, a potent vasodilator released by endothelial cells, inhibits platelet aggregation and adhesion to vascular endothelial surfaces. Because endothelial cell damage is considered pivotal in the pathogenesis of preeclampsia, this study was initiated to determine whether nitric oxide production is decreased in patients with preeclampsia.


METHODS
Twenty-six patients with preeclampsia (as defined by a blood pressure > or = 140 mm Hg systolic or 90 mm Hg diastolic plus proteinuria, > or = 300 mg per 24 hours or > or = 2+ by dipstick, both occurring on two occasions > or = 4 hours apart) and 26 normotensive women with singleton gestations in the third trimester were studied. Because nitric oxide is spontaneously oxidized to both nitrite and nitrate, two analytic assays were used serially. Serum nitrite levels were initially determined with the Greiss reagent and subsequently analyzed with Escherichia coli nitrate reductase.


RESULTS
With the Greiss reagent alone the mean +/- SEM of serum nitrite level in 26 patients with preeclampsia was significantly decreased compared with 26 normotensive patients (3.46 +/- 1.43 mumol/L vs 4.65 +/- 0.85 mumol/L, p = 0.02). With the addition of the nitrate reductase enzyme of Escherichia coli the mean +/- SEM of serum nitrite level in 26 preeclamptic patients was again significantly decreased compared with 26 normotensive patients (20.04 +/- 1.25 mumol/L vs 27.38 +/- 2.23 mumol/L, p = 0.02). One patient with the syndrome of hemolysis, elevated liver enzymes, and low platelets demonstrated a concurrent decrease in serum nitrite over a 2-week period, emphasizing the relationship of nitric oxide to the pathophysiologic features of the syndrome.


CONCLUSIONS
Circulating levels of nitrite are decreased in patients with preeclampsia. These data support the concept that diminished nitric oxide synthesis contributes to the pathophysiologic changes seen in preeclampsia.
Seligman
S P
SP
Department of Obstetrics and Gynecology, New York University Medical Center, NY 10016.
Buyon
J P
JP
Clancy
R M
RM
Young
B K
BK
Abramson
S B
SB
D000328:Adult; D001794:Blood Pressure; D005260:Female; D017359:HELLP Syndrome / Q000097:blood; D006801:Humans; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D011225:Pre-Eclampsia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide