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 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.
Manunta
P
P
Division of Nephrology, Dialysis, and Hypertension, University "Vita Salute San Raffaele", Milan, Italy. manunta.paolo@hsr.it
Messaggio
E
E
Ballabeni
C
C
Sciarrone
M T
MT
Lanzani
C
C
Ferrandi
M
M
Hamlyn
J M
JM
Cusi
D
D
Galletti
F
F
Bianchi
G
G
D000328:Adult; D001794:Blood Pressure; D002298:Cardenolides; D018592:Cross-Over Studies; D004077:Digoxin; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D012083:Renin / Q000097:blood; D012503:Saponins / Q000097:blood*; D012964:Sodium / Q000378:metabolism*
D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D004077:Digoxin; D012964:Sodium; D012083:Renin