Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats

Furosemide and hydrochlorothiazide (HCTZ) exert their diuretic actions by binding to apical Na+ transporters, viz., the Na+-K+-2Cl− cotransporter in the thick ascending limb and the Na+-Cl−cotransporter in the distal convoluted tubule, respectively. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic administration of furosemide or HCTZ is associated with compensatory changes in the abundance of Na+ transporters downstream from the primary site of action. Osmotic minipumps were implanted into Sprague-Dawley rats to deliver furosemide (12 mg/day) or HCTZ (3.75 mg/day) for 7 days. To prevent volume depletion, all animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. The diuretic/natriuretic response was quantified in response to both agents by using quantitative urine collections. Semiquantitative immunoblotting revealed that the abundances of thick ascending limb Na+-K+-2Cl− cotransporter and all ...