An
ouabain-like factor has been implicated repeatedly in
salt-sensitive
hypertension as a
natriuretic agent. However, the response of plasma
ouabain-like factor to acute and chronic variation of body
sodium is unclear. We studied 138 patients with
essential hypertension who underwent an acute volume expansion/contraction maneuver (2 days) and 20 patients who entered a blind randomized crossover design involving chronically controlled
sodium intake and depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, plasma levels of
ouabain-like factor were higher during
sodium depletion (acute: 338.8+/-17.4 and 402.7+/-22.8 pmol/L for baseline and low
sodium, respectively, P<0.01; chronic: 320.4+/-32.0 versus 481.0+/-48.1 pmol/L, P=0.01). No significant change in plasma
ouabain-like factor was observed after a 2-hour saline infusion (333.4+/-23.9 pmol/L) or controlled
sodium (402.1+/-34.9 pmol/L). When patients were divided into
salt-sensitive or
salt-resistant groups, no differences in plasma
ouabain-like factor were observed in the 2 groups at baseline or in response to the 2 protocols:
salt resistant (n=69, 340.1+/-25.9 pmol/L) versus
salt sensitive (n=69, 337.4+/-23.6 pmol/L) and chronic
salt resistant (n=11, 336.0+/-53.2) versus
salt sensitive (n=9, 301.1+/-331.4 pmol/L). However, circulating
ouabain-like factor was increased by
sodium depletion in both groups. These results demonstrate that circulating
ouabain-like factor is raised specifically by maneuvers that promote the loss of body
sodium. Acute expansion of body fluids with isotonic saline is not a stimulus to plasma
ouabain-like factor. Moreover, basal levels of plasma
ouabain-like factor do not differ among patients with
salt-sensitive or
salt-resistant
hypertension. Taken together, these new results suggest that
ouabain-like factor is involved in the adaptation of humans to
sodium depletion and argue against the hypothesis that
ouabain-like factor is a
natriuretic hormone.