Ouabain and serum sodium.

Ouabain and Serum Sodium To the Editor: Sodium-dependent mechanisms play a role in the pathogenesis of hypertension. He et al recently demonstrated that in normotensive and hypertensive subjects an acute reduction in salt intake, from 350 to 10 mmol/d for 5 days, was associated with a decline in serum sodium by 3 mmol/L. Conversely, a progressive increase in salt intake from 10 to 250 mmol/d by a daily amount of 50 mmol caused an increase in serum sodium in normotensive subjects, but not hypertensive patients.1 These investigators speculated that small changes in serum sodium might directly affect the hypothalamic control of blood pressure through the local pituitary renin-angiotensin system.1 Ouabain is a steroid hormone, which is released from the hypothalamus and the adrenal gland. It is implicated in sodium homeostasis and exerts direct actions on the vasculature, the heart,2 and tubular sodium reabsorption.3 In individuals randomly recruited from a Flemish population, blood pressure increased by 2.2 mm Hg systolic and 1.4 mm Hg diastolic for each 50-mmol/d increment in urinary sodium excretion when the plasma ouabain concentration was below the median (140 pmol/L).4 No association between blood pressure and urinary sodium was found when plasma ouabain exceeded the median.4 In the same population,4 we tried to reproduce He’s observations in 369 subjects not using treatment with diuretics. Blood pressure was the average of 5 consecutive readings obtained at each of 2 home visits 4 to 6 weeks apart. The study sample included 48.0% men, 30.9% current smokers, and 25.5% hypertensive patients. Mean age was 39.8 16.7 (SD) years. Mean values for systolic/diastolic blood pressure, serum sodium, and the 24-hour urinary sodium excretion were 123 15/ 77 11 mm Hg, 141.6 2.5 mmol/L, and 192 61 (range, 24 to 391) mmol/d, respectively. The geometric mean concentration of plasma ouabain was 145 (95% confidence interval, 138 to 148) pmol/L. With adjustment for sex, age, body mass index, and current smoking, serum sodium did not increase with sodium excretion (partial r 0.01, P 0.88). However, with similar adjustments, we found an independent and positive relation between the serum concentrations of sodium and ouabain with a partial correlation coefficient of 0.12 (95% confidence interval, 0.02 to 0.22, P 0.03). In a sensitivity analysis only including 334 untreated subjects, the partial correlation coefficient was 0.11 (95% confidence interval, 0.00 to 0.22, P 0.06). This relation was stronger in men than in women (r 0.18 versus r 0.03, respectively; P 0.001). In conclusion, our observational study in Flemish subjects free from antihypertensive therapy did not confirm that serum sodium increased with urinary sodium excretion. However, in line with the perspectives of He’s recent article,1 we noticed that the serum sodium concentration, which is a tightly regulated variable, is positively and independently correlated with plasma ouabain, a hypothalamic and adrenal hormone. Further research should assess whether this association is direct, whether it is mediated via extracellular volume or endocrine factors, and whether it is different in women and men.