Endogenous Ligand of α 1 Sodium Pump, Marinobufagenin, Is a Novel Mediator of Sodium Chloride–Dependent Hypertension

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Abstract
Background— Digitalis-like sodium pump ligands (SPLs) effect natriuresis via inhibition of renal tubular Na+,K+-ATPase but may induce vasoconstriction. The present study investigated the potential roles of 2 putative endogenous SPLs, an ouabain-like compound (OLC) and an α1 Na+,K+-ATPase inhibitor, marinobufagenin (MBG), in regulating natriuresis and blood pressure (BP) responses to sustained and acute NaCl loading in Dahl salt-sensitive rats (DS). Methods and Results— During 4 weeks of an 8% NaCl diet, DS exhibited a progressive increase in MBG renal excretion (66±13 pmol/24 hours at week 4 versus 11±1 pmol/24 hours at baseline, n=48), which paralleled an increase in systolic BP (174±10 mm Hg at week 4 versus 110±2 mm Hg at baseline). By contrast, OLC excretion peaked at week 1 and returned to baseline levels. Administration of an anti-MBG, but not anti-ouabain antibody, to DS after 3 weeks of a high NaCl diet lowered BP (139±7 versus 175±5 mm Hg, PConclusions— An initial transient stimulation of OLC induced by NaCl loading of DS precedes an MBG response. A sustained increase in MBG production in DS contributes to the chronic BP elevation induced by a sustained high NaCl intake.