Endothelin-1 inhibits sodium reabsorption by ETAand ETBreceptors in the mouse cortical collecting duct

May 24, 2013American journal of physiology. Renal physiology

Endothelin-1 reduces sodium absorption in the mouse kidney’s outer collecting duct through ET(A) and ET(B) receptors

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Abstract

Transepithelial sodium reabsorption (JNa) in the collecting duct is significantly inhibited by endothelin-1 (ET-1).

The collecting duct shows substantial JNa that is partly regulated by a pathway sensitive to benzamil, likely involving the epithelial sodium channel (ENaC).
JNa is greater in the cortical collecting duct (CCD) compared to the outer medullary collecting duct (OMCD).
Benzamil-insensitive JNa occurs in the CCD but is absent in the OMCD.
In the presence of ET-1, ENaC-mediated JNa is significantly inhibited.
Blockade of ETA or ETB receptors restores JNa to control rates, with ETA receptor blockade specifically restoring the benzamil-sensitive component of JNa.
Na reabsorption in the CCD is mediated by both ENaC-dependent and ENaC-independent mechanisms.

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The collecting duct (CD) is a major renal site for the hormonal regulation of Na homeostasis and is critical for systemic arterial blood pressure control. Our previous studies demonstrated that the endothelin-1 gene (edn1) is an early response gene to the action of aldosterone. Because aldosterone and endothelin-1 (ET-1) have opposing actions on Na reabsorption (JNa) in the kidney, we postulated that stimulation of ET-1 by aldosterone acts as a negative feedback mechanism, acting locally within the CD. Aldosterone is known to increase JNa in the CD, in part, by stimulating the epithelial Na channel (ENaC). In contrast, ET-1 increases Na and water excretion through its binding to receptors in the CD. To date, direct measurement of the quantitative effect of ET-1 on transepithelial JNa in the isolated in vitro microperfused mouse CD has not been determined. We observed that the CD exhibits substantial JNa in male and female mice that is regulated, in part, by a benzamil-sensitive pathway, presumably ENaC. ENaC-mediated JNa is greater in the cortical CD (CCD) than in the outer medullary CD (OMCD); however, benzamil-insensitive JNa is present in the CCD and not in the OMCD. In the presence of ET-1, ENaC-mediated JNa is significantly inhibited. Blockade of either ETA or ETB receptor restored JNa to control rates; however, only ETA receptor blockade restored a benzamil-sensitive component of JNa. We conclude 1) Na reabsorption is mediated by ENaC in the CCD and OMCD and also by an ENaC-independent mechanism in the CCD; and 2) ET-1 inhibits JNa in the CCD through both ETA and ETB receptor-mediated pathways.

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Endothelin-1 inhibits sodium reabsorption by ETAand ETBreceptors in the mouse cortical collecting duct

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