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.
Sandrim
Valeria C
VC
Santa Casa de Belo Horizonte, Núcleo de Pós-Graduação, Av. Francisco Sales, 1111, 30150-221, Belo Horizonte, MG, Brazil.
Montenegro
Marcelo F
MF
Palei
Ana C T
AC
Metzger
Ingrid F
IF
Sertorio
Jonas T C
JT
Cavalli
Ricardo C
RC
Tanus-Santos
Jose E
JE
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