ETB Receptor in Renal Medulla Is Enhanced by Local Sodium During Low Salt Intake

Renal endothelin-1 participates in sodium and water handling, and its urinary excretion is increased in sodium-retentive states. We compared the cortical and medullary renal expression of prepro-endothelin-1, endothelin-converting enzyme-1, and endothelin type A and type B receptors in patients who underwent nephrectomy after normal (108 mmol/d NaCl; n=6) or low (20 mmol/d NaCl; n=6) sodium diet and investigated whether sodium exerts a direct role on endothelin receptor binding in vitro. With normal sodium diet prepro-endothelin-1 mRNA was 3-fold higher in renal medulla than in cortex (P <0.01), whereas endothelin-converting enzyme-1 mRNA was equally distributed. Endothelin-1 receptor density was 2-fold higher in renal medulla than in cortex (P <0.05). Type B was the main receptor subtype in both regions. In the renal cortex, low sodium diet caused a 194% increase in prepro-endothelin-1 mRNA (P <0.05), whereas endothelin-converting enzyme-1 type B and type A receptors remained unchanged. In contrast, in the renal medulla the increase in prepro-endothelin-1 mRNA (+30%, P <0.05) was associated with a selective increase in type B receptor for both mRNA expression (+37%, P <0.05) and binding density (+55%, P <0.05). Increasing in vitro sodium concentrations between 154 and 308 mmol/L significantly enhanced type B receptor density (P <0.05) and affinity (P <0.05). In conclusion, during low sodium diet, renal prepro-endothelin-1 synthesis increases mainly in the renal cortex (where no changes in receptors occur), whereas type B receptor is selectively enhanced in the renal medulla. The range of sodium concentrations that are physiologically present in vivo in the renal medulla selectively modulate type B receptor density and affinity.