Na⁺ leak in erythrocytes from essential hypertensive patients

1. Ouabain- and bumetanide-resistant (OBR) Na⁺ efflux from human erythrocytes into a Mg²⁺-sucrose medium exhibits kinetic properties consistent with a transmembrane Na⁺ leak.

2. In 52 essential hypertensive patients, the rate constant of Na⁺ leak (k_e) was 15.0 ± 2.9 × 10⁻³h⁻¹ (mean ±sd). This was significantly higher than the k_e in 47 normotensive controls (13.2 ± 1.6 × 10⁻³h⁻¹; t = 3.81, P < 0.001; Mann-Whitney U rank sum test P = 0.0014). The relatively small number of patients studied was insufficient to decide if the hypertensive population was bi-modally distributed. Nevertheless, if the upper end of the normotensive population is used as a cutoff point, it appears that a subgroup of 12 hypertensive patients had an increased Na⁺ leak, k_e = 19.5 ± 1.9 × 10⁻³ h⁻¹ (mean±sd). The increased Na⁺ leak remained constant in repeated determinations over several months.

3. Na⁺ movements catalysed by the Na⁺-K⁺ co-transport and Na⁺-Li⁺ countertransport systems were measured in the above 52 hypertensive patients. Seventeen hypertensive patients showed a low apparent affinity of the co-transport system for internal Na⁺ and 12 exhibited a high maximal rate of Na⁺-Li⁺ countertransport. None of these two abnormalities was found in the 12 hypertensive patients with increased k_e. We propose to denote them as Leak-(+) hypertensive patients.

4. Passive net Na⁺ entry was abnormally high in all Leak-(+) hypertensive patients. However, erythrocyte Na⁺ content was increased in only five of the 12 Leak-(+) hypertensive patients. A normal or even decreased Na⁺ content was associated with the presence of compensatory increases in the maximal rate of the Na⁺-K⁺ pump and the Na⁺-K⁺ co-transport system.