Effect of acute saline volume expansion in the anaesthetised DeltaF508 cystic fibrosis mouse.
It has been suggested that CFTR Cl(-) channels in the renal inner medullary collecting duct may be involved in mediating increased renal salt excretion during extracellular fluid volume expansion. To investigate this hypothesis, in-vivo clearance experiments were performed comparing wild-type (WT) and DeltaF508-CFTR transgenic mice (cftr (tm2Cam)). Control animals were given a 0.1-ml bolus of 0.9% saline, followed by I.V. infusion at 0.3 ml x h(-1). Volume expansion was applied by infusing a 1-ml bolus of 0.9% saline followed by infusion at 0.6 ml x h(-1). No significant differences in renal NaCl handling between WT mice ( C(Na)=1.2 +/- 0.3 microl x min(-1), C(Cl)=4.0 +/- 0.5 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=1.7 +/- 0.5 microl x min(-1), C(Cl)=4.1 +/- 0.8 microl x min(-1)) were observed under control conditions. Volume expansion resulted in large significant increases in NaCl clearance in both WT mice ( C(Na)=7.0 +/- 0.9 microl x min(-1), C(Cl)=12.0 +/- 0.6 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=7.2 +/- 1.6 microl x min(-1), C(Cl)=11.0 +/- 2.2 microl x min(-1)). However, there was no significant difference between WT and DeltaF508-CFTR mice. In conclusion, renal NaCl excretion is not significantly different under basal conditions and during saline volume expansion in DeltaF508-CFTR mice. The data suggest that CFTR is not a physiologically important mediator of volume natriuresis.
Kibble
J D
JD
Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. j.kibble@sheffield.ac.uk
Neal
A
A
Green
R
R
Colledge
W H
WH
Taylor
C J
CJ
D000758:Anesthesia; D000818:Animals; D001810:Blood Volume / Q000502:physiology*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D007668:Kidney / Q000502:physiology; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D009318:Natriuresis / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride