Evidence for cystic fibrosis transmembrane conductance regulator‐dependent sodium reabsorption in kidney, using Cftrtm2cammice
JD Kibble, AM Neal, WH Colledge… - The Journal of …, 2000 - Wiley Online Library
JD Kibble, AM Neal, WH Colledge, R Green, CJ Taylor
The Journal of Physiology, 2000•Wiley Online Library1 The aims of this study were to investigate (a) if renal Na+ handling was normal in
Cftrtm2camΔF508 cystic fibrosis mice,(b) whether adaptation to dietary salt depletion was
preserved and (c) whether Cftrtm2camΔF508 mice exhibited enhanced amiloride‐sensitive
Na+ absorption. 2 In Na+‐replete animals (maintained on a 0.32% NaCl diet) given a 150
mM NaCl iv maintenance infusion, there was no difference in fractional Na+ excretion
(FENa) between wild‐type (0.42±0.06%, n= 12) and Cftrtm2camΔF508 mice (0.47±0.13 …
Cftrtm2camΔF508 cystic fibrosis mice,(b) whether adaptation to dietary salt depletion was
preserved and (c) whether Cftrtm2camΔF508 mice exhibited enhanced amiloride‐sensitive
Na+ absorption. 2 In Na+‐replete animals (maintained on a 0.32% NaCl diet) given a 150
mM NaCl iv maintenance infusion, there was no difference in fractional Na+ excretion
(FENa) between wild‐type (0.42±0.06%, n= 12) and Cftrtm2camΔF508 mice (0.47±0.13 …
- 1The aims of this study were to investigate (a) if renal Na+ handling was normal in Cftrtm2camΔF508 cystic fibrosis mice, (b) whether adaptation to dietary salt depletion was preserved and (c) whether Cftrtm2camΔF508 mice exhibited enhanced amiloride‐sensitive Na+ absorption.
- 2In Na+‐replete animals (maintained on a 0.32 % NaCl diet) given a 150 mM NaCl i.v. maintenance infusion, there was no difference in fractional Na+ excretion (FENa) between wild‐type (0.42 ± 0.06 %, n= 12) and Cftrtm2camΔF508 mice (0.47 ± 0.13 %, n= 7). Amiloride infusion significantly increased FENa in both wild‐type (3.14 ± 0.83 %, n= 6) and Cftrtm2camΔF508 mice (3.47 ± 0.63 %, n= 9), though with no significant difference between genotypes.
- 3A 14 day dietary salt restriction (animals maintained on a 0.03 % NaCl diet) and maintenance infusion with a 15 mM NaCl vehicle caused a reduction in FENa to 0.14 ± 0.05 %, n= 8 in wild‐type mice and 0.14 ± 0.04 %, n= 8 in Cftrtm2camΔF508 mice. No significant difference in the ability to adapt to low salt conditions was apparent comparing the two genotypes.
- 4Treatment of salt‐restricted mice with amiloride resulted in a blunted natriuresis in both wild‐type mice (FENa= 1.10 ± 0.16 %, n= 7) and Cftrtm2camΔF508 mice (FENa= 1.97 ± 0.29 %, n= 9). The natriuresis induced by amiloride was significantly greater in Cftrtm2camΔF508 mice than in wild‐type controls.
- 5In conclusion, Cftrtm2camΔF508 mice exhibit normal renal salt excretion when either salt replete or salt restricted. Enhanced amiloride‐sensitive FENa is consistent with increased Na+ absorption via the amiloride‐sensitive sodium channel ENaC, in cystic fibrosis kidney, but this was only observed during salt restriction.
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