BackgroundWe have previously reported the isolation from human placentas of an inhibitor of the sodium pump (Na/K ATP-ase) of molecular weight 370 Da, which is considered to have a dihydropyrone-substituted steroid (bufenolide) structure.ObjectiveTo examine if this inhibitor is present outside of the pregnant state.MethodsWe examined the plasma ultrafiltrate of patients who were clinically volume-expanded. During the period of this study five such patients were identified. One was receiving haemofiltration for acute renal failure and four were being treated by plasma exchange. High performance liquid chromatograph (HPLC) purified fractions obtained from each of these five patients inhibited the human leucocyte sodium pumpin vitro.ResultsEach of the purified fractions that inhibited the leucocyte ATP-asein vitrocontained a compound of mass 370 Da, the same mass as that found previously in placental extracts. This inhibitory factor was absent from HPLC purified fractions of plasma ultrafiltrate obtained from fifty-five patients who were clinically normovolaemic. Negative ion mass spectrometry (MS)/MS of the inhibitory material produced the fragmentation pattern characteristic of the placenta-derived pump inhibitor in only one of the five samples. The other four samples, although having the same mass, exhibited a different fragmentation pattern.ConclusionThe results suggest that an inhibitor of the sodium pump, identical in mass to that obtained from human placentas, circulates in the plasma of volume-expanded patients. The fragmentation pattern observed in negative ion mass spectrometry in the majority of the volume expanded patients may represent the presence of an isomer of the sodium pump inhibitor previously described in placental material.