Na-K-Cl cotransporters and salt-sensitive hypertension

In the 80s, erythrocyte Na-K-Cl cotransporter of essential hypertensive was reported: (i) decreased in fresh erythrocytes and (ii) increased, followin g repeated cell washings and incubations. This suggested to us that the man ipulation of erythrocytes (from essential hypertensives) was able to dissoc iate a cotransport inhibitory factor, thus unmasking up-regulation of membr ane cotransport units. This working hypothesis was recently confirmed in Da hl salt-sensitive rats (DS). The primary defect of DS rats seems to be hyperactivity of cotransporter Na -K-CI BSC1 at the thick ascending limb of Henle's loop (TAL). Moreover, ora l salt-loading induces an abnormally high increase in the urinary and plasm atic ClF levels of DS rats. The increase in urinary CIF excretion seems to be a compensatory mechanism, able to reduce BSC1 hyperactivity and NaCl rea bsorption at the TAL. The increase in plasmatic CIF should inhibit erythroc yte BSC2, thus inducing "up-regulation" of the membrane density of cotransp ort proteins. Further studies are required to test this model in human with "salt-sensiti ve" hypertension.