A digoxin-like factor associates with erythrocyte sodium concentration, sodium transport, and ouabain binding

To investigate what effects a circulating digoxin-like factor (DLF) might have on sodium metabolism, we examined data collected on 1,327 individuals screened in the Cardiovascular Genetics Clinic at the University of Utah. This sample included 639 unmedicated adults, 582 youths under age 18, and 106 medicated hypertensive individuals, all on an unrestricted diet when attending clinic. No individuals look digitalis. A digoxin assay detected measurable levels of plasma DLF in 13.4% of the youths, 17.2% of the normotensive adults, and 25.5% of the hypertensive adults. In all three groups of individuals, those with a measurable DLF had a significantly lower erythrocyte ouabain sensitive sodium efflux rate constant (adjusted for age, sex and body mass) than those with no measurable DLF (p less than 0.01). Normotensive and hypertensive adults with measurable DLF also had an increased erythrocyte intracellular sodium level. Either the number of ouabain binding sites and/or the apparent affinity for ouabain were reduced for those with DLF levels in all three groups. There was a small nonsignificant increase in blood pressure for the normotensive adults and youths with a measurable DLF. We conclude that plasma DLF is associated with reduced ouabain sensitive sodium transport and increased intracellular sodium concentration, possibly due to changes in the number of or the competition for the Na+ - K+ ATPase sites.