Increased circulating cell-free hemoglobin levels reduce nitric oxide bioavailability in preeclampsia

Abstract

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.