ANG II provokes acute trafficking of distal tubule Na+-Cl(-) cotransporter to apical membrane

Am J Physiol Renal Physiol. 2007 Sep;293(3):F662-9. doi: 10.1152/ajprenal.00064.2007. Epub 2007 May 16.


The distal convoluted tubule (DCT) Na+-Cl(-) cotransporter (NCC), the target of thiazide diuretics, is responsible for the reabsorption of 5-10% of filtered NaCl. The aim of this study was to test the hypothesis that acute infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril (at 12 microg/min) for 20 min provokes trafficking of NCC from apical plasma membranes (APM) to subapical cytoplasmic vesicles (SCV), which is reversed by acute ANG II infusion (ANG II at 20 along with 12 microg/min captopril) for 20 min in male Sprague-Dawley rats (250-350 g). By immuno-electron microscopy using an anti-NCC (D. Ellison) 71.5 +/- SD 4.9% of the NCC gold labeling was associated with the APM in control, sham operated, and infused rats, while captopril infusion reduced NCC in APM to 54.9 +/- 6.9% (P < 0.001) and markedly increased immunogold labeling of SCV. Subsequent infusion of ANG II with captopril restored NCC immunogold labeling of APM to 72.4 +/- 4.2%, that is, 20% of the total NCC trafficked between APM and SCV. Likewise, on density gradients of cortex, captopril provoked redistribution of 27.3% of total NCC from low-density APM-enriched membranes to higher-density membranes and ANG II+captopril restored 20.3% of the NCC to APM-enriched fractions. Redistribution occurred independent of a change in NCC total abundance. In conclusion, this study demonstrates that ACE inhibition provokes acute trafficking of NCC out of the plasma membrane, which likely decreases DCT Na+ reabsorption, while ANG II provokes rapid trafficking of NCC from stores in subapical vesicles to the plasma membrane, which likely increases DCT Na+ reabsorption.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Captopril / pharmacology
  • Gene Expression Regulation
  • Kidney Tubules, Distal / cytology
  • Kidney Tubules, Distal / drug effects
  • Kidney Tubules, Distal / metabolism*
  • Microscopy, Immunoelectron
  • Protein Transport
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism*
  • Sodium Chloride Symporters / genetics
  • Sodium Chloride Symporters / metabolism*


  • Angiotensin-Converting Enzyme Inhibitors
  • Receptors, Drug
  • Sodium Chloride Symporters
  • thiazide receptor
  • Angiotensin II
  • Captopril