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Am J Physiol Renal Physiol 284: F11-F21, 2003; doi:10.1152/ajprenal.00119.2002
0363-6127/03 $5.00
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Vol. 284, Issue 1, F11-F21, January 2003

TRANSLATIONAL PHYSIOLOGY
Loop diuretics: from the Na-K-2Cl transporter to clinical use

Sudha S. Shankar and D. Craig Brater

Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202-5124

The diuretic response to loop diuretics in various disease states has consistently been found to be subnormal. One of the key determinants of the degree of diuretic response is the functional integrity of the sodium-potassium-chloride transporter in the loop of Henle. Studies in animal models suggest that expression/activity of the transporter may be affected by factors such as altered natural splicing events of NKCC2 (the gene encoding for the renal transporter), renal prostanoids, vasopressin, and other autacoids. We have reviewed the pharmacokinetics and pharmacodynamics of loop diuretics in health and in edematous disorders for which they are used. On the basis of evidence reviewed in this paper, we propose that altered expression or activity of the sodium-potassium-chloride transporter in the loop of Henle, in conjunction with events occurring in other segments of the nephron, possibly accounts for the altered diuretic response to these agents. Thus the modulators of this altered expression/activity could serve as important therapeutic targets for alternative diuretic regimens in these conditions.

edematous disorders; furosemide


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