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Angiotensin II provokes acute trafficking of Distal Na+/Cl‐ cotransporter (NCC)
Author(s) -
sandberg monica birgitta,
maunsbach arvid b,
mcdonough alicia a
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1227-d
Subject(s) - captopril , endocrinology , medicine , distal convoluted tubule , cotransporter , renin–angiotensin system , angiotensin ii , apical membrane , chemistry , membrane , sodium , kidney , reabsorption , receptor , biochemistry , organic chemistry , blood pressure
The distal convoluted tubule (DCT) Na+‐Cl− cotransporter (NCC) reabsorbs 5–10% of filtered NaCl and is the target of thiazide diuretics used to treat hypertension. NCC abundance is known to be regulated by aldosterone; the role of angiotensin II (AngII) in NCC regulation is less well defined. We previously reported that high salt diet provokes chronic redistribution of DCT NCC from apical to subapical membranes (Hypertension 46: 884). This study aimed at testing the hypothesis that inhibition of AngII production provokes acute redistribution of NCC to subapical membranes and that this effect is reversed by AngII infusion. Inactin anesthetized male Sprague Dawley rats (250–350 g) were infused with ACE inhibitor captopril via the jugular vein (12 ug/min) for 20 min. Half the rats were subsequently infused with both captopril (12ug/min) and AngII (20ng·kg‐1·min‐1) for 20 min. Paired controls were sham‐operated and infused. Kidneys were excised, cortex dissected, homogenized and fractionated on sorbitol density gradients. NCC was detected with anti‐TSC (D. Ellison) in the fractions by immunoblot. Compared to the control where NCC peak in low density membranes (associated with apical distribution by EM), acute captopril caused a marked redistribution of NCC to higher density membranes (associated with subapical distribution by EM). Subsequent infusion of AngII with captopril restored NCC distribution to low density apical membranes. In conclusion, this study provides evidence for acute trafficking of NCC from low density apical to higher density subapical membranes during ACE inhibition and reversal from subapical to apical membranes when systemic AngII is restored. Supported by DK34316