Effects of renal denervation on the NKCC2 cotransporter in the thick ascending limb of the loop of Henle in rats with congestive heart failure

Diuretic drugs are used almost universally in patients with congestive heart failure, most frequently the potent loop diuretics. Despite their unproven effect on survival, their indisputable efficacy in relieving congestive symptoms makes them first line therapy for most patients. In the treatment of more advanced stages of heart failure diuretics may fail to control salt and water retention despite the use of appropriate doses. Diuretic resistance may be caused by decreased renal function and reduced and delayed peak concentrations of loop diuretics in the tubular fluid, but it can also be observed in the absence of these pharmacokinetic abnormalities. When the effect of a short acting diuretic has worn off, postdiuretic salt retention will occur during the rest of the day. Chronic treatment with a loop diuretic results in compensatory hypertrophy of epithelial cells downstream from the thick ascending limb and consequently its diuretic effect will be blunted. Strategies to overcome diuretic resistance include restriction of sodium intake, changes in dose, changes in timing, and combination diuretic therapy. DOI: http://dx.doi.org/10.3329/jdnmch.v17i1.12193 J. Dhaka National Med. Coll. Hos. 2011; 17 (01): 44-46

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Losartan treatment normalizes renal sodium and water handling in rats with mild congestive heart failure

AJP Renal Physiology ◽

10.1152/ajprenal.00132.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. F307-F315 ◽

Cited By ~ 24

Author(s):

Dennis Staahltoft ◽

Søren Nielsen ◽

Nadeem R. Janjua ◽

Sten Christensen ◽

Ole Skøtt ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Renal Function ◽

Sodium Excretion ◽

Thick Ascending Limb ◽

Receptor Blockade ◽

Water Reabsorption ◽

Aquaporin 2 ◽

Henle's Loop ◽

Losartan Treatment

This study was designed to examine the effect of losartan treatment on renal tubular function in rats with mild congestive heart failure (CHF) induced by ligation of the left anterior descending artery. In rats with CHF, there was a significant decrease in daily sodium excretion, which caused sodium retention relative to control rats. Renal function studies revealed that glomerular filtration rate and proximal tubular sodium handling were normal. However, expression of the Na+-K+-2Cl− cotransporter (NKCC2) in the thick ascending limb of Henle's loop was increased. Moreover, vasopressin-mediated renal water reabsorption, as evaluated by the aquaretic response to selective V2-receptor blockade, was significantly increased. Losartan treatment normalized expression of NKCC2 and decreased expression of the vasopressin-regulated water channel aquaporin-2. This was associated with normalization of daily sodium excretion and normalization of the aquaretic response to V2-receptor blockade. Together, these results indicate that, in rats with CHF, losartan treatment inhibits increased sodium reabsorption through NKCC2 in the thick ascending limb of Henle's loop and water reabsorption through aquaporin-2 in the collecting ducts, which may be involved in improving renal function in losartan-treated CHF rats.

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Role of renal nerves in sodium retention of cirrhosis and congestive heart failure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.2.r298 ◽

1991 ◽

Vol 260 (2) ◽

pp. R298-R305 ◽

Cited By ~ 18

Author(s):

G. F. DiBona ◽

L. L. Sawin

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Renal Denervation ◽

Bile Duct Ligation ◽

Renal Nerves ◽

Coronary Artery Ligation ◽

Common Bile Duct Ligation ◽

Artery Ligation ◽

Duct Ligation

To define the role of renal nerves in renal Na retention of cirrhosis and congestive heart failure (CHF), experiments were done in rats with cirrhosis due to common bile duct ligation (CBDL) and CHF due to myocardial infarction from left coronary artery ligation. Two weeks after induction of CBDL or CHF, diseased and sham diseased (Sham) rats were subjected to bilateral renal denervation (DNX) or sham renal denervation (innervated, INN). Five days after DNX or INN, 26-day metabolic balance studies were carried out in all rats. Daily dietary Na intake averaged 2.0-3.0 meq/day on days 1-6 and 22-26 and averaged 0.120 meq/day on days 7-21. Cumulative Na balance was greater in CBDL and CHF rats, INN or DNX, than in Sham/CBDL or CHF rats throughout the study. On day 6 at the end of the normal dietary Na intake period (days 0-6), cumulative Na balance was not affected by renal denervation in Sham/CBDL or CHF rats (INN, 2.02 +/- 0.19 meq, n = 10; DNX, 2.04 +/- 0.17 meq, n = 11), CBDL rats (INN, 4.21 +/- 0.39 meq, n = 10; DNX, 3.78 +/- 0.37 meq, n = 10), or CHF rats (INN, 3.74 +/- 0.72 meq, n = 9; DNX, 3.22 +/- 0.55 meq, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

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