Marinobufagenin, an endogenous ligand of alpha-1 sodium pump, is a marker of congestive heart failure severity.
BACKGROUND
A reduced cardiac output in chronic heart failure (CHF) evokes renal NaCl and water retention, and, therefore, activates mechanisms promoting natriuresis. Atrial natriuretic peptide (ANP) is one such factor. We hypothesized that another NaCl sensitive endogenous natriuretic factor, i.e., marinobufagenin (MBG), a specific ligand of the alpha-1 subunit of Na/K ATPase (the main kidney isoform) and also a vasoconstrictor and cardiotonic substance, would be elevated in CHF patients in a graded manner with the severity of CHF.


RESULTS
We measured the plasma levels of MBG, alpha-hANP, ouabain-like compound (OLC) and left ventricular (LV) volumes and ejection fraction in 23 consecutive hypertensive male patients with CHF. Plasma MBG levels exhibited progressive increases (0.59 +/- 0.15, 1.08 +/- 0.20, 1.35 +/- 0.17 and 1.88 +/- 0.05 nmol/l NYHA 1-4, respectively) and paralleled the changes of alpha-hANP. Conversely, plasma OLC did not exhibit such increases. Plasma MBG correlated with alpha-hANP (r = 0.82; P < 0.0001). Both MBG and alpha-hANP correlated with LV systolic (r = 0.55 and r = 0.47; P < 0.01) diameter and inversely with ejection fraction (r = -0.73 and r = -0.60; P < 0.01). OLC did not exhibit correlations with alpha-hANP or LV volumes, but positively correlated with systolic brachial blood pressure and with pulse pressure.


CONCLUSIONS
In CHF, MBG exhibits progressive increases similar to ANP, varies with CHF severity and correlates with LV systolic function. We hypothesize, that, in CHF, the concurrent production of these two natriuretic hormones, a vasorelaxant, ANP, and a vasoconstrictor, MBG, potentiate each other's natriuretic effects, but may offset their vasoactive actions.
Fridman
Alexander I
AI
Laboratory of Cardiovascular Science, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Matveev
Sergei A
SA
Agalakova
Natalia I
NI
Fedorova
Olga V
OV
Lakatta
Edward G
EG
Bagrov
Alexei Y
AY
D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001810:Blood Volume; D001916:Brachial Artery / Q000503:physiopathology; D002018:Bufanolides / Q000097:blood*; D002298:Cardenolides; D004077:Digoxin / Q000097:blood; D004791:Enzyme Inhibitors / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D012503:Saponins / Q000097:blood; D012720:Severity of Illness Index; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013318:Stroke Volume; D013599:Systole; D014662:Vasoconstrictor Agents / Q000097:blood*; D016277:Ventricular Function, Left
D015415:Biomarkers; D002018:Bufanolides; D002298:Cardenolides; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008024:Ligands; D012503:Saponins; D014662:Vasoconstrictor Agents; C034504:digoxin-like factors; C093896:marinobufagenin; D004077:Digoxin; D009320:Atrial Natriuretic Factor; D000254:Sodium-Potassium-Exchanging ATPase