Which diuretic primarily targets the ascending limb of the loop of Henle?

• A. Furosemide
• B. Hydrochlorothiazide
• C. Spironolactone
• D. Acetazolamide

Answer: (A)

Loop diuretics act on the thick ascending limb of the loop of Henle by inhibiting the Na+-K+-2Cl− (NKCC2) cotransporter there. Blocking this transporter prevents reabsorption of Na, Cl, and K in that segment, and it also collapses the medullary concentrating gradient, leading to a potent diuresis with increased excretion of Na, Cl, K, Ca, and Mg. Furosemide is the classic loop diuretic that does exactly this, so it best fits the description of targeting the ascending limb.

Other diuretics act at different nephron sites: hydrochlorothiazide inhibits NaCl reabsorption in the distal convoluted tubule; spironolactone is a potassium-sparing diuretic acting in the collecting duct by blocking aldosterone receptors; acetazolamide inhibits carbonic anhydrase in the proximal tubule, causing bicarbonate diuresis.