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(Hypertension. 2001;38:198.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Plasma Ouabain-Like Factor During Acute and Chronic Changes in Sodium Balance in Essential Hypertension

Paolo Manunta; Elisabetta Messaggio; Cinzia Ballabeni; Maria Teresa Sciarrone; Chiara Lanzani; Mara Ferrandi; John M. Hamlyn; Daniele Cusi; Ferruccio Galletti; Giuseppe Bianchi; for the Salt Sensitivity Study Group of the Italian Society of Hypertension

From the Division of Nephrology, Dialysis, and Hypertension, University "Vita Salute San Raffaele" (P.M., E.M., C.B., M.T.S., C.L.), Milan, Italy; Prassis Research Institute Sigma-Tau, Settimo Milanese (M.F.), Milan, Italy; Department of Physiology, School of Medicine, University of Maryland (J.M.H.), Baltimore; Division of Nephrology University of Milan (D.C.), Milan, Italy; Department of Experimental Medicine, University of Naples, Federico II (F.G.), Naples, Italy.

Correspondence to Paolo Manunta, MD, Division of Nephrology, Dialysis, and Hypertension, University "Vita e Salute" San Raffaele, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy. E-mail manunta.paolo{at}hsr.it

Abstract— 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.

Key Words: sodium pump inhibitor • endogenous • salt sensitivity • high blood pressure

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