Increased circulating cell-free hemoglobin levels reduce nitric oxide bioavailability in preeclampsia.
Contrasting with increased nitric oxide (NO) formation during healthy pregnancy, reduced NO bioavailability plays a role in preeclampsia. However, no study has examined whether increased NO consumption by enhanced circulating levels of cell-free hemoglobin plays a role in preeclampsia. We studied 82 pregnant women (38 healthy pregnant and 44 with preeclampsia). To assess NO bioavailability, we measured plasma and whole blood nitrite concentrations using an ozone-based chemiluminescence assay. Plasma ceruloplasmin concentrations and plasma NO consumption (pNOc) were assessed and plasma hemoglobin (pHb) concentrations were measured with a commercial immunoassay. We found lower whole blood and plasma nitrite concentrations in preeclamptic patients (-48 and -39%, respectively; both P<0.05) compared with healthy pregnant women. Plasma samples from preeclamptic women consumed 63% more NO (P=0.003) and had 53% higher pHb and 10% higher ceruloplasmin levels than those found in healthy pregnant women (P<0.01). We found significant positive correlations between pHb and pNOc (r=0.61; P<0.0001), negative correlations between pNOc and whole blood or plasma nitrite concentrations (P=0.02; r=-0.32 and P=0.01; r=-0.34, respectively), and negative correlations between pHb and whole blood or plasma nitrite concentrations (P=0.03; r=-0.36 and P=0.01; r=-0.38, respectively). These findings suggest that increased pHb levels lead to increased NO consumption and lower NO bioavailability in preeclamptic compared with healthy pregnant women.
Santa Casa de Belo Horizonte, Núcleo de Pós-Graduação, Av. Francisco Sales, 1111, 30150-221, Belo Horizonte, MG, Brazil.
Valeria C
VC
Sandrim
Marcelo F
MF
Montenegro
Ana C T
AC
Palei
Ingrid F
IF
Metzger
Jonas T C
JT
Sertorio
Ricardo C
RC
Cavalli
Jose E
JE
Tanus-Santos
D000328:Adult; D001682:Biological Availability; D002570:Ceruloplasmin / Q000032:analysis; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000097:blood / Q000493:pharmacokinetics*; D009573:Nitrites / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D000091402:Prohibitins
D006454:Hemoglobins; D009573:Nitrites; C000717328:PHB protein, human; D000091402:Prohibitins; D009569:Nitric Oxide; D002570:Ceruloplasmin