An endogenous digitalis-like compound extracted from human urine: biochemical and chemical studies.
Plasma and urine levels of an endogenous digitalis-like compound (EDLC) are increased in low renin Na+-dependent experimental hypertension, in some normotensive offspring of hypertensive patients and in some essential hypertensive patients. Urine-drived EDLC was purified from 550 L of urine from essential hypertensive patients (n = 8) and from normotensive subjects with a family history of hypertension (n = 27), using flash chromatography on C18 reversed-phase, anion exchange chromatography and various reversed-phase high performance liquid chromatographies. The mechanism of Na+-K+ ATPase inhibition and the related effects of semipurified urine-derived EDLC were studied and compared with those of ouabain. Its action was similar to that of ouabain in 8 out of 10 of the tests applied. The main effects of such a compound were the depression of Na+-K+ pump activity of human erythrocytes, the inhibition of 5-hydroxytryptamine reuptake by human platelets, and the induction of natriuresis in urethanized rats. Therefore, EDLC may be considered as one of the natriuretic hormones whose mechanism of action closely resembles that of ouabain.
Cloix
J F
JF
Département de pharmacologie, INSERM U7 CNRS UA318, Hôpital Necker, Paris, France.
Crabos
M
M
Grichois
M L
ML
Meyer
P
P
D000328:Adult; D000818:Animals; D001798:Blood Proteins / Q000302:isolation & purification / Q000494:pharmacology / Q000652:urine*; D002298:Cardenolides; D002851:Chromatography, High Pressure Liquid; D004077:Digoxin; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012503:Saponins; D012701:Serotonin / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000097:blood
D001798:Blood Proteins; D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D012701:Serotonin; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase