Regulation of sodium transport in the proximal tubule by endothelin.

Human essential hypertension and rodent genetic hypertension are associated with increased sodium transport in the renal proximal tubule and medullary thick ascending limb of Henle. The proximal tubule, which secretes endothelin (ET), expresses the ET(B) receptor. Low (nM) concentrations of ET, via the ET(B) receptor, inhibit sodium and water transport and ATP-driven drug secretion in the proximal tubule. In contrast, very low (pM) and high nM concentrations of ET increase renal proximal sodium transport, but the receptor involved remains to be determined. The natriuretic effect of ET(B) receptor stimulation is impaired in spontaneously hypertensive rats, due in part to a defective interaction with D(3) dopamine and angiotensin II type 1 receptors. Impaired ET(B) receptor function in the renal proximal tubule may be important in the pathogenesis of genetic hypertension.