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Loop diuretics: from the Na-K-2Cl transporter to clinical use
Sudha S Shankar1, D Craig Brater
1Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5124, USA.
American Journal of Physiology. Renal Physiology
|December 11, 2002
Summary
Loop diuretics are less effective in certain diseases due to changes in the sodium-potassium-chloride transporter. Targeting this transporter may lead to new diuretic treatments.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- The diuretic response to loop diuretics is often reduced in various disease states.
- The sodium-potassium-chloride transporter (NKCC2) in the loop of Henle is crucial for diuretic efficacy.
Purpose of the Study:
- To review the pharmacokinetics and pharmacodynamics of loop diuretics in health and edematous disorders.
- To propose a mechanism for the subnormal diuretic response in disease states.
Main Methods:
- Literature review of pharmacokinetic and pharmacodynamic studies.
- Analysis of evidence regarding factors affecting NKCC2 expression/activity in animal models.
- Synthesis of information on loop diuretic response in edematous disorders.
Main Results:
- Loop diuretic response is consistently subnormal in various disease states.
- NKCC2 expression/activity may be altered by factors including splicing events, prostanoids, and vasopressin.
- Altered expression/activity of NKCC2, along with nephron segment events, likely contributes to reduced diuretic response.
Conclusions:
- Altered expression or activity of the sodium-potassium-chloride transporter in the loop of Henle is a key factor in diminished loop diuretic response.
- Modulating NKCC2 expression/activity presents potential therapeutic targets for alternative diuretic strategies.
- Further research into these modulators could improve treatment for edematous conditions.