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Published Online
on June 23, 2008

Hypertension. 2008
Published online before print June 23, 2008, doi: 10.1161/HYPERTENSIONAHA.108.115006
A more recent version of this article appeared on August 1, 2008
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Submitted on April 16, 2008
Revised on May 19, 2008

Nitric Oxide Formation Is Inversely Related to Serum Levels of Antiangiogenic Factors Soluble Fms-Like Tyrosine Kinase-1 and Soluble Endogline in Preeclampsia

Valeria C. Sandrim; Ana C.T. Palei; Ingrid F. Metzger; Valeria A. Gomes; Ricardo C. Cavalli; and Jose E. Tanus-Santos*

From the Departments of Pharmacology (V.C.S., I.F.M., J.E.T-S.) and Gynecology and Obstetrics (R.C.C.), Faculty of Medicine of Ribeirao Preto, and Department of Pharmacology (A.C.T.P, V.A.G.), Faculty of Medical Sciences, State University of Campinas, Sao Paulo, Brazil.

* To whom correspondence should be addressed. E-mail: tanus{at}fmrp.usp.br.

Abstract—Deficient NO formation has been implicated in hypertensive disorders of pregnancy. However, no previous study has compared the circulating nitrite concentrations in healthy pregnant women with those found in hypertensive disorders of pregnancy. Moreover, 2 antiangiogenic factors produced in the placenta (soluble fms-like tyrosine kinase-1 and soluble endogline) may affect NO formation during pregnancy. Here, we hypothesized that lower concentrations of markers of NO formation exist in hypertensive disorders of pregnancy and that inverse relationships exist between these markers and soluble fms-like tyrosine kinase-1 or soluble endogline. In this cross-sectional study, we compared 58 healthy pregnant women with 56 gestational hypertensive subjects and 45 preeclamptic patients. We measured plasma and whole blood nitrite concentrations using an ozone-based chemiluminescence assay and serum soluble fms-like tyrosine kinase-1 and soluble endogline concentrations using enzyme immunoassays. Whole blood nitrite levels were significantly lower in gestational hypertensive subjects and preeclamptic patients (-36% and -58%, respectively; both P<0.05) compared with healthy pregnant women. The plasma nitrite levels were {approx}37% lower in both groups with hypertensive disorders of pregnancy compared with the group with normotensive pregnancies (both P<0.05). As expected, we found higher circulating soluble fms-like tyrosine kinase-1 and soluble endogline concentrations in preeclampsia compared with gestational hypertensive subjects or with healthy pregnancies (both P<0.05). We found negative correlations between antiangiogenic factors and plasma or whole blood nitrite concentrations (Spearman's r from -0.175 to -0.226; all P<0.05). Our results show clinical evidence for impaired NO formation in preeclampsia or gestational hypertension. The negative correlations between markers of NO formation and antiangiogenic factors in preeclamptic patients suggest an inhibitory effect for these factors on NO formation.


Key words: NO • nitrite • whole blood nitrite • preeclampsia • sEng • sFLT-1




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