Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis

Na+ reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K+ excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K+ balance. The pathways are int...

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Main Authors:	Hunter, Robert W., Craigie, Eilidh, Homer, Natalie Z. M., Mullins, John J., Bailey, Matthew A.
Format:	Online
Language:	English
Published:	American Physiological Society 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920023/

id	pubmed-3920023
recordtype	oai_dc
spelling	pubmed-39200232014-08-05 Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis Hunter, Robert W. Craigie, Eilidh Homer, Natalie Z. M. Mullins, John J. Bailey, Matthew A. Articles Na+ reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K+ excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K+ balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na+ channel (ENaC) downstream. This effect might be mediated by changes in distal Na+ delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na+ flux through ENaC, with a concomitant increase in renal K+ excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K+ excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na+ reabsorption was not normally limited by Na+ delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na+ restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na+ reabsorption through ENaC solely by increasing distal Na+ delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments. American Physiological Society 2014-01-08 2014-02-15 /pmc/articles/PMC3920023/ /pubmed/24402096 http://dx.doi.org/10.1152/ajprenal.00339.2013 Text en Copyright © 2014 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0 (http://creativecommons.org/licenses/by/3.0/deed.en_US) : the American Physiological Society.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hunter, Robert W. Craigie, Eilidh Homer, Natalie Z. M. Mullins, John J. Bailey, Matthew A.
spellingShingle	Hunter, Robert W. Craigie, Eilidh Homer, Natalie Z. M. Mullins, John J. Bailey, Matthew A. Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis
author_facet	Hunter, Robert W. Craigie, Eilidh Homer, Natalie Z. M. Mullins, John J. Bailey, Matthew A.
author_sort	Hunter, Robert W.
title	Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis
title_short	Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis
title_full	Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis
title_fullStr	Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis
title_full_unstemmed	Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis
title_sort	acute inhibition of ncc does not activate distal electrogenic na+ reabsorption or kaliuresis
description	Na+ reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K+ excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K+ balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na+ channel (ENaC) downstream. This effect might be mediated by changes in distal Na+ delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na+ flux through ENaC, with a concomitant increase in renal K+ excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K+ excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na+ reabsorption was not normally limited by Na+ delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na+ restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na+ reabsorption through ENaC solely by increasing distal Na+ delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments.
publisher	American Physiological Society
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920023/
_version_	1612056950683467776

Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis

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