Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis.
This study was designed to examine the effect of bilateral renal denervation (DNX) on thick ascending limb of Henle's loop (TAL) function in rats with liver cirrhosis induced by common bile duct ligation (CBL). The CBL rats had, as previously shown, sodium retention associated with hypertrophy of the inner stripe of the outer medulla (ISOM) and increased natriuretic effect of furosemide in vivo, and semiquantitative immunoblotting showed increased expression of the furosemide-sensitive Na-K-2Cl cotransporter type 2 (NKCC2) in ISOM from CBL rats. DNX significantly attenuated the sodium retention in the CBL rats, which was associated with normalization of the natriuretic effect of furosemide, as well as a significant reduction in the expression of NKCC2 in the ISOM. However, the marked hypertrophy of the ISOM found in CBL rats was not reversed by DNX. Together, these data indicate that increased renal sympathetic nerve activity known to be present in CBL rats plays a significant role in the formation of sodium retention by stimulating sodium reabsorption in the TAL via increased renal abundance of NKCC2.
Jonassen
Thomas E N
TE
Department of Pharmacology, University of Copenhagen, DK-2200 Copenhagen N, Denmark. fitj@farmakol.ku.dk
Brønd
Lone
L
Torp
Malene
M
Graebe
Martin
M
Nielsen
Søren
S
Skøtt
Ole
O
Marcussen
Niels
N
Christensen
Sten
S
D000450:Aldosterone / Q000097:blood; D000818:Animals; D003135:Common Bile Duct / Q000502:physiology; D003714:Denervation; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000378:metabolism; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1
D004232:Diuretics; C578716:Slc12a1 protein, rat; D012982:Sodium, Dietary; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D000450:Aldosterone; D005665:Furosemide; D012964:Sodium; D012083:Renin