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1 Department of Pharmacology, University of Copenhagen, DK-2200 Copenhagen N; 2 The Water and Salt Research Center, Institute of Anatomy, and 4 University Institute of Pathology, Aarhus Kommune Hospital, University of Aarhus, DK-8000 Aarhus C; and 3 Department of Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense C, Denmark
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.
common bile duct ligation; furosemide-sensitive sodium-potassium-2chloride cotransporter type 2; thick ascending limb; furosemide; sodium balance; inner stripe of outer medulla
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