Is the circulating ouabain-like compound ouabain?

The evidence is very strong for a circulating inhibitor of the sodium, potassium ATPase in volume-expanded hypertension. Recently, this inhibitor was isolated from human plasma and identified as ouabain. We are reporting our results using a very specific and sensitive immunoassay for ouabain with which we were unable to detect or able to detect only very low levels of circulating immunoreactive ouabain. Immunoassay of 5 mL of human and rat plasma, incubation fluid from bovine and human adrenal cell cultures extracted using a C-18 solid phase column, and HPLC separation did not detect a peak corresponding to ouabain. This procedure could easily detect authentic ouabain added to these extracts at a concentration slightly below that reported to be present by others. The extract from the adrenal cultures had clearly detectable sodium, potassium ATPase using an assay based on inhibition of tritiated ouabain binding to human red cells. Extraction of bovine adrenals detected a very small amount of immunoassayable ouabain which did not elute at a time corresponding to that of ouabain. This study indicates that the postulated sodium, potassium ATPase inhibitor that circulates in plasma is not ouabain, but it is likely to be structurally similar to ouabain, as it appears to cross-react with some antibodies against ouabain.