Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension.

Abstract

Sodium-sensitive hypertension is thought to be dependent on primary alterations in renal tubular sodium reabsorption. The major apical plasma membrane Na(+) transporters include the proximal tubular Na(+)-H(+) exchanger, the thick ascending limb Na(+)-K(+)-2Cl(-) cotransport system, the distal tubular Na(+)-Cl(-) cotransporter, and the collecting duct epithelial sodium channel (ENaC). This article explores the role of each transporter in the pathogenesis of hypertension. Although the contribution of the proximal tubule Na(+)-H(+) exchanger is not yet defined completely, more convincing data have been generated about the importance of the Na(+)-K(+)-2Cl(-). Indeed at least 2 forms of hypertension appear to be related to the up-regulation of the transporter: the so-called programmed hypertension induced by low-protein diet during pregnancy and the early phase of hypertension in the Milan strain of rats. With respect to the Na(+)-Cl(-) cotransporter this may be overactive caused by inactivating mutation of WNK4 as in the Gordon syndrome, although it is the main actor for the maintenance phase of the hypertension found in the Milan strain of rats. Finally, the contribution of the ENaC has been established clearly; indeed, in the Liddle syndrome the mutation of the ENaC gene leads to a longer retention of the channel on the cell surface of collecting duct principal cells, thus inducing stronger sodium reabsorption along this segment. All these examples clearly indicate that renal sodium transporters may be responsible for various types of sodium-sensitive hypertension.

• Authors: Giovambattista Capasso, Alessandra Cantone, Ciriana Evangelista, Miriam Zacchia, Francesco Trepiccione, Daria Acone, Maria Rizzo
• Journal: Seminars in nephrology (Semin Nephrol) Vol. 25 Issue 6 Pg. 419-24 (Nov 2005) ISSN: 0270-9295 [Print] United States
• PMID: 16298266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Sodium Channels
• Sodium Chloride Symporters
• Sodium-Potassium-Chloride Symporters

Topics

• Animals
• Disease Models, Animal
• Female
• Hypertension (physiopathology)
• Hypertension, Renal (physiopathology)
• Kidney Function Tests
• Male
• Rats
• Rats, Inbred SHR
• Sensitivity and Specificity
• Sodium Channels (metabolism)
• Sodium Chloride Symporters (physiology)
• Sodium-Potassium-Chloride Symporters (physiology)
• Up-Regulation