[Na-K-Cl cotransporters and "salt-sensitive" arterial hypertension]

In the 80s, erythrocyte Na-K-Cl cotransporter of essential hypertensive was reported: (i) decreased in fresh erythrocytes and (ii) increased, following repeated cell washings and incubations. This suggested to us that the manipulation of erythrocytes (from essential hypertensives) was able to dissociate a cotransport inhibitory factor, thus unmasking up-regulation of membrane cotransport units. This working hypothesis was recently confirmed in Dahl salt-sensitive rats (DS). The primary defect of DS rats seems to be hyperactivity of cotransporter Na-K-Cl BSC1 at the thick ascending limb of Henle's loop (TAL). Moreover, oral salt-loading induces an abnormally high increase in the urinary and plasmatic CIF levels of DS rats. The increase in urinary CIF excretion seems to be a compensatory mechanism, able to reduce BSC1 hyperactivity and NaCl reabsorption at the TAL. The increase in plasmatic CIF should inhibit erythrocyte BSC2, thus inducing "up-regulation" of the membrane density of cotransport proteins. Further studies are required to test this model in human with "salt-sensitive" hypertension.