Association of increased erythrocyte Na+/H+ exchanger with renal Na+ retention in patients with essential hypertension

The goal of this study was to investigate the activity of the Na+/H+ exchanger in erythrocytes of patients with essential hypertension and its relation with urinary Na+ excretion. The study was performed in cells from 27 untreated hypertensive patients and 30 normotensive controls with similar age and sex distribution. All subjects were studied after 4 days on a controlled Na+ diet (145 mmol/ day). The activity of the Na+/H+ exchanger was determined by acidifying cell pH and measuring the initial rate of the net Na+-dependent H+ efflux. The activity of the Na+/H+ exchanger was higher in hypertensive patients than in controls (301 ± 45 v 162 ± 23 mmol/L cells/h, mean ± SEM; P< .01). With the upper limit of the normotensive population as a cut-off point (385 mmol/L cells/h), a subgroup of 12 hypertensive patients had an abnormally high activity of Na+/H+ exchanger. Compared with controls and with patients with normal exchanger activity, patients with increased exchanger activity were characterized by lower net (P< .01) and fractional (P< .05) Na+ excretion. The accumulative Na+ balance was higher (P< .01) in hypertensive patients with increased activity of the exchanger (39.90 ± 3.47 mmol) than in the remaining hypertensive patients (0.59 ± 6.96 mmol) or in the normotensive population (−5.71 ± 6.12 mmol). After analyzing the relationship of renin activity with Na+ excretion it was observed that renin activity was inappropriately low in 9 (75%) patients with increased exchanger, in 6 (40%) patients with normal exchanger, and in 6 (20%) normotensives, these differences being significant (P< .01). A reciprocal correlation was found between the activity of the exchanger and plasma renin activity in the group of hypertensive patients (r = 0.60, P< .001). These results indicate that increased activity of the erythrocyte Na+/H+ exchanger is associated with increased tubular Na+ reabsorption, Na+ retention, and low renin secretion in a subgroup of essential hypertensive patients. These findings suggest that erythrocyte Na+/H+ exchanger overactivity may be a marker of deranged Na+ handling in essential hypertension.