Effect of Volume Expansion on the Natriuretic Response to Ouabain Infusion

Abstract

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 µg 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 µmol 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 digitalislike factor, would support a possible physiological role for endogenous digitalislike factor in the regulation of sodium homeostasis.

Carbonylation Modification Regulates Na/K-ATPase Signaling and Salt Sensitivity: A Review and a Hypothesis

“…In vivo experiments suggest the essential role of endogenous CTS in modulating renal sodium excretion and BP with different approaches. First, administration of some (e.g., ouabain) but not all CTS induces natriuresis (Foulkes et al, 1992 ; Yates and McDougall, 1995 ). Second, in transgenic mice expressing ouabain-sensitive Na/K-ATPase α1 subunit, both acute salt load and ouabain infusion augment natriuretic responses, which may be inhibited by administration of an anti-digoxin antibody fragment (Dostanic-Larson et al, 2005 ; Loreaux et al, 2008 ).…”

Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

“…Although their pathophysiological significance has been a subject of debate for many years [65], the concept of a natriuretic hormone is supported by the experimental observations in animal models of ouabain-induced natriuresis [66, 67]. Recently, several elegant reports have confirmed this concept with different approaches.…”

Physiological roles of endogenous ouabain in normal rats

“…8, 9, and 42). Indeed, administration of ouabain to sheep or to isolated rats kidneys resulted in marked natriuresis (16,49). Recently, Loreaux and coworkers (28) showed that transgenic mice expressing ouabain-sensitive ␣ 1 -Na ϩ -K ϩ -ATPase augmented the natriuretic response to acute salt load.…”