Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles

• Published in: American journal of physiology. Renal physiology 2009-04, Vol.296 (4), p.F810-F818
• Main Authors: Lee, Donna H, Riquier, Anne D M, Yang, Li E, Leong, Patrick K K, Maunsbach, Arvid B, McDonough, Alicia A
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Acute Disease; Angiotensin II - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Animals; Blood pressure; Blood Pressure - drug effects; Captopril - administration & dosage; Cell Fractionation; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cytoplasm; Cytoplasmic Vesicles - drug effects; Cytoplasmic Vesicles - metabolism; Cytoplasmic Vesicles - ultrastructure; Disease Models, Animal; Diuresis - drug effects; Hypertension; Hypertension - metabolism; Hypertension - physiopathology; Infusions, Intravenous; Kidney Tubules, Distal - drug effects; Kidney Tubules, Distal - metabolism; Kidney Tubules, Distal - ultrastructure; Kidneys; Male; Microscopy; Microscopy, Immunoelectron; Protein Transport; Rats; Rats, Sprague-Dawley; Receptors, Drug - metabolism; Salt; Sodium; Sodium Chloride Symporters - metabolism; Solute Carrier Family 12, Member 3; Symporters - metabolism; Time Factors
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.90606.2008

When blood pressure (BP) is elevated above baseline, a pressure natriuresis-diuresis response ensues, critical to volume and BP homeostasis. Distal convoluted tubule Na(+)-Cl(-) cotransporter (NCC) is regulated by trafficking between the apical plasma membrane (APM) and subapical cytoplasmic vesicles (SCV). We aimed to determine whether NCC trafficking contributes to pressure diuresis by decreasing APM NCC or compensates for increased volume flow to the DCT by increasing APM NCC. BP was raised 50 mmHg (high BP) in rats by arterial constriction for 5 or 20-30 min, provoking a 10-fold diuresis at both times. Kidneys were excised, and NCC subcellular distribution was analyzed by 1) sorbitol density gradient fractionation and immunoblotting and 2) immunoelectron microscopy (immuno-EM). NCC distribution did not change after 5-min high BP. After 20-30 min of high BP, 20% of NCC redistributed from low-density, APM-enriched fractions to higher density, endosome-enriched fractions, and, by quantitative immuno-EM, pool size of APM NCC decreased 14% and SCV pool size increased. Because of the time lag of the response, we tested the hypothesis that internalization of NCC was secondary to the decrease in ANG II that accompanies high BP. Clamping ANG II at a nonpressor level by coinfusion of captopril (12 microg/min) and ANG II (20 ng.kg(-1).min(-1)) during 30-min high BP reduced diuresis to eightfold and prevented redistribution of NCC from APM- to SCV-enriched fractions. We conclude that DCT NCC may participate in pressure natriuresis-diuresis by retraction out of apical plasma membranes and that the retraction is, at least in part, driven by the fall in ANG II that accompanies acute hypertension.