Circulating sodium pump inhibitors in five volume-expanded humans.
BACKGROUND
We 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.


OBJECTIVE
To examine if this inhibitor is present outside of the pregnant state.


METHODS
We 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 pump in vitro.


RESULTS
Each of the purified fractions that inhibited the leucocyte ATP-ase in vitro contained 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.


CONCLUSIONS
The 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.
McKinnon
William
W
Renal Laboratory, St Thomas' Hospital, London, UK.
Lord
Gwyn A
GA
Forni
Lui G
LG
Hilton
Philip J
PJ
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D045604:Extracellular Fluid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006440:Hemofiltration; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008970:Molecular Weight; D010953:Plasma Volume / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000097:blood*
D015415:Biomarkers; D000254:Sodium-Potassium-Exchanging ATPase