A Labile Endogenous Na-pump Inhibitor in Man

Abstract

A circulating, endogenous sodium pump inhibitor (ESPI) has been implicated in the pathogenesis of essential hypertension (3). Efforts to identify this factor have generated a bewildering array of chemically different candidates (1). Previous efforts to isolate such a factor for further characterization have used techniques, which while appropriate for the purification of stable chemical species, have been too long and/or ineffective in protecting chemically labile species. We have developed a procedure to purify ESPI from human fluids that would be rapid and provide protection for air and thermally sensitive chemical species to ascertain whether such compounds exist and to allow for their study. We had previously carried out a clinical study in which we isolated an ESPI from human peritoneal dialysate (PD) from patients with sustained extracellular fluid volume expansion (6). PD levels of this ESPI were correlated with volume status, blood pressure, and serum Na⁺/K⁺-ATPase inhibitory activity. Additionally, it appeared to be chemically unstable. We have continued to use this same paradigm to insure isolation of a volume-sensitive ESPI and to exploit PD as a source because it is rapidly available and readily processed.