Excretion of artifactual endogenous digitalis-like factors.
Radioimmunoassays have been used to detect digoxin-like immunoreactive factors (DLF) in the plasma and urine of hypertensive patients and rats with deoxycorticosterone acetate (DOCA)-salt hypertension. Uninephrectomized rats (n = 9), given 15 mg DOCA . kg-1 . wk-1, were fed a standard rat chow supplemented with 2% NaCl (DOCA-HS); control animals (n = 15) were given vehicle injection and a specially formulated low-salt diet (0.05% NaCl). At 4 wk, DOCA-HS rats were hypertensive (121.4 +/- 10.1 vs. 88 +/- 4.4 Torr, mean +/- SEM, P less than 0.05) and excreted more DLF (2.7 +/- 1.1 vs. 0.2 +/- 0.1 ng digoxin equivalents . day-1, P less than 0.001) compared with control rats. DLF, partially purified from DOCA-HS urine by antidigoxin antibody immunoaffinity chromatography, was found to have a molecular weight less than 2,000, was resistant to acid hydrolysis or proteases, and had many properties of the cardiac glycosides, including inhibition of Na+-K+-ATPase activity, displacement of ouabain from human erythrocyte membranes, and inhibition of 86Rb influx into red blood cells. When DOCA-HS rats were switched to the low-sodium chow, DLF excretion dropped precipitously. No measurable DLF (less than 10 pg/ml) was detected in the plasma of rats eating either chow. However, greater than 95% of the urinary DLF could be attributed to a contaminant in the standard laboratory chow; rats fed the low-salt chow supplemented with 2% NaCl excreted much less DLF, and DLF was isolated from the standard chow.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002846:Chromatography, Affinity; D003900:Desoxycorticosterone / Q000494:pharmacology; D004077:Digoxin / Q000032:analysis*; D004910:Erythrocyte Membrane / Q000201:enzymology; D005189:False Positive Reactions; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D003900:Desoxycorticosterone; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium