Salt intake and depletion increase circulating levels of endogenous ouabain in normal men

High-salt diets elevate circulating
Na+ pump inhibitors, vascular resistance, and blood pressure.
Ouabain induces a form of hypertension mediated via the alpha2-Na+ pump
isoform and the calcium influx mode of the vascular sodium calcium
exchanger (NCX). Whereas elevated levels of an endogenous ouabain
(EO) and NCX have been implicated in salt-sensitive hypertension, acute
changes in sodium balance do not affect plasma EO. This study investigated
the impact of longer-term alterations in sodium balance on the
circulating levels and renal clearance of EO in normal humans. Thirteen
normal men consumed a normal diet, high-salt diet, and hydrochlorothiazide
(HCTZ), each for 5-day periods to alter sodium balance. EO and
other humoral and urinary variables were determined daily. On a normal
diet, urinary sodium excretion (140 16 meq/day), plasma EO (0.43
0.08 nmol/l) and urinary EO excretion (1.04 0.13 nmol/day) were at
steady state. On the 3rd day of a high-salt diet, urine sodium excretion
(315 28 meq/day), plasma EO (5.8 2.2 nmol/l), and the urinary EO
excretion (1.69 0.27 nmol/day) were significantly increased, while
plasma renin activity and aldosterone levels were suppressed. The saltevoked
increase in plasma EO was greater in older individuals, in
subjects whose baseline circulating EO was higher, and in those with low
renal clearance. During HCTZ, body weight decreased and plasma renin
activity, aldosterone, and EO (1.710.77 nmol/l) rose, while urinary EO
excretion remained within the normal range (1.44 0.31 nmol/day).
Blood pressure fell in one subject during HCTZ. HPLC of the plasma
extracts showed one primary peak of EO immunoreactivity with a
retention time equivalent to ouabain. High-salt diets and HCTZ raise
plasma EO by stimulating EO secretion, and a J-shaped curve relates
sodium balance and EO in healthy men. Under normal dietary conditions,
98% of the filtered load of EO is reabsorbed by the kidney, and
differences in the circulating levels of EO are strongly influenced by
secretion and urinary excretion of EO. The dramatic impact of high-salt
diets on plasma EO is consistent with its proposed role as a humoral
vasoconstrictor that links salt intake with vascular function in hypertension.