Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertension

An ouabain-like factor has been implicated repeatedly in salt-sensitive hyp ertension as a natriuretic agent. However, the response of plasma ouabain-l ike factor to acute and chronic variation of body sodium is unclear. We stu died 138 patients with essential hypertension who underwent an acute volume expansion/contraction maneuver (2 days) and 20 patients who entered a blin d randomized crossover design involving chronically controlled sodium intak e and depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, p lasma levels of ouabain-like factor were higher during sodium depletion (ac ute: 338.8 +/- 17.4 and 402.7 +/- 22.8 pmol/L for baseline and low sodium, respectively, P<0.01; chronic: 320.4<plus/minus>32.0 versus 481.0 +/- 48.1 pmol/L, P=0.01). No significant change in plasma ouabain-like factor was ob served 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-sensi tive 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 protocol s: 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 o uabain-like factor was increased by sodium depletion in both groups. These results demonstrate that circulating ouabain-like factor is raised specific ally 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 f actor. Moreover, basal levels of plasma ouabain-like factor do not differ a mong patients with salt-sensitive or salt-resistant hypertension. Taken tog ether, these new results suggest that ouabain-like factor is involved in th e adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone.