Role of ceruloplasmin in nitric oxide metabolism in plasma of humans and sheep: a comparison of adults and fetuses

Nitric oxide (NO) is metabolized in plasma, in part by the ferroxidase ceruloplasmin (Cp), to form nitrite and nitrosothiols (SNOs), which are proposed to mediate protective responses to hypoxia and ischemia. We hypothesized that NO metabolism would be attenuated in fetal plasma due to low Cp activity. We measured Cp concentrations and activity in plasma samples collected from adults and fetuses of humans and sheep. We then added NO ([NO]: 1.5 or 100 μM) to plasma and aqueous buffer and measured rates of NO disappearance and the production of nitrite and SNO. Cp concentrations in fetal plasma were <15% of adult levels. In aqueous buffer, 1.5 μM NO disappeared with a half-life of 347 ± 64 s (means ± SE) but in plasma of humans the half-life was 19 ± 2 s (adult) and 11 ± 1 s (fetus, P = 0.004) and in sheep it was 31 ± 3 s (adult) and 43 ± 5 s (fetus, P = 0.04). Cp activity was not correlated with the overall elimination half-life of NO or with the amount of SNO ([NO]: 100 μM) or nitrite ([NO]: 1.5 or 100 μM) produced but correlated with SNO yields at 1.5 μM [NO] (r = 0.92, P = 0.04). Our data demonstrate that Cp is not essential to the increased rate of metabolism of NO in plasma relative to aqueous buffers and that it is not essential to the production of nitrite from NO. Cp may be involved in the conversion of NO to SNO in plasma under near-physiological concentrations of NO.