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Published Online
on July 8, 2002

Hypertension. 2002
Published online before print July 8, 2002, doi: 10.1161/01.HYP.0000026809.68674.F9
A more recent version of this article appeared on August 1, 2002
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Right arrow Physiological and pathological control of gene expression

Submitted on February 4, 2002
Revised on February 25, 2002

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

Simone Vanni; Gianluca Polidori; Ilaria Cecioni; Sergio Serni; Marco Carini; and Pietro Amedeo Modesti*

From the Clinica Medica e Cardiologia (S.V., G.P., I.C., P.A.M.), and the Division of Urology (S.S., M.C.), University of Florence, Italy.

* To whom correspondence should be addressed. E-mail: pa.modesti{at}dfc.unifi.it.

Abstract—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.


Key words: endothelin • receptors, endothelin • sodium • kidney • water-electrolyte balance • diet, sodium-restricted




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