= Loop diuretic
A \b[loop diuretic] is a <diuretic> whose principal renal action reduces salt reabsorption in the <thick ascending limb> of the <Loop of Henle>. Drugs such as <bumetanide> and <furosemide> inhibit the coupled sodium–potassium–chloride transport system associated with <NKCC2>. Less reabsorption leaves more salt available for excretion and changes the kidney's handling of water.<Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney by G. Gamba and others>[Kidney Na-K-Cl transporter, bumetanide sensitivity and functional expression.]{ref} https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32dfbea3-eb2b-4070-8605-57ce3e6d5a2f[Bumex prescribing information, Clinical Pharmacology: ascending-limb sodium/chloride reabsorption and clearance measurements]{ref}
The location can be tested directly. <M. Imai> compared the drugs on isolated rabbit and rat thick ascending limbs perfused in vitro. Luminal application reversibly suppressed the lumen-positive <electric potential difference>; bumetanide also reduced measured chloride-tracer efflux. An isolated-segment assay links the response to local tubular transport, rather than relying only on the final urine volume of a whole animal.<Effect of bumetanide and furosemide on the thick ascending limb of Henle's loop of rabbits and rats perfused in vitro by M. Imai>[1977 abstract: luminal application, reversible potential change and chloride efflux.]{ref}
The tracer and electrical readouts are complementary: a change in potential is evidence about the coupled epithelial system, while a tracer measurement follows movement of a particular ion. Neither is itself a direct atomic image of a drug-binding pocket.
An idealized balance makes the downstream consequence clear. If a fixed filtered salt amount is 100 units and total reabsorption falls from 98 to 95 units with every other contribution held fixed, excretion rises from 2 to 5 units. This illustrates amplification of a small fractional reabsorption change; it is not a prediction of a dose response or a clinical treatment rule.
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