ANG II provokes acute trafficking of distal tubule Na+-Cl(-) cotransporter to apical membrane.
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 ng.kg(-1).min(-1) 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.
Sandberg
Monica B
MB
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Riquier
Anne D M
AD
Pihakaski-Maunsbach
Kaarina
K
McDonough
Alicia A
AA
Maunsbach
Arvid B
AB
D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D005786:Gene Expression Regulation; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D049992:Sodium Chloride Symporters / Q000235:genetics / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011955:Receptors, Drug; D049992:Sodium Chloride Symporters; C064415:thiazide receptor; D000804:Angiotensin II; D002216:Captopril