Effect of volume expansion on the natriuretic response to ouabain infusion

Evidence exists that an endogenous substance which inhibits (Na+,K+)-ATPase, in a similar manner to the cardiac glycosides, may have important cardiovascular and renal effects. Whilst ouabain or a closely related isomer has been reported to be present in mammalian plasma, renal effects of ouabain occur only at high concentrations. The effect of expansion of blood volume on the renal response to ouabain infusion was examined in conscious sheep. Five sheep with catheters chronically implanted into the renal artery received four treatment combinations in random order: (I) vehicle (0.15 mol l-1 NaCl) infusion; (II) 500 micrograms ouabain infused into the renal artery over 60 min; (III) 500 ml 6% dextran 70 in 0.9% saline infused intravenously, and (IV) the dextran and ouabain treatments together. Treatment with either ouabain or plasma volume expansion produced modest increases in sodium excretion and urine flow. Treatment with ouabain when combined with plasma volume expansion increased sodium excretion from 82 +/- 30 to 880 +/- 203 mumol min-1 and urine flow from 1.9 +/- 1.1 to 7.5 +/- 1.6 ml min-1. This combination of treatments results in a synergistic rather than additive response. This study indicates that under some circumstances the response of the kidney to inhibition of (Na+,K+)-ATPase can be enhanced and, if inhibition can be demonstrated to occur at physiologically relevant concentrations of endogenous digitalis-like factor, would support a possible physiological role for endogenous digitalis-like factor in the regulation of sodium homeostasis.