Metabolic acidosis has dual effects on sodium handling by rat kidney.
Chronic metabolic acidosis (CMA) is associated with decreased NaCl reabsorption in the proximal tubule (PT). However, the effect of CMA on Na(+) transport in the distal tubule (DT) and collecting duct (CD) is poorly understood. Rats were placed in metabolic cages and had access to water (control), 0.28 M NH(4)Cl, or 0.28 M KCl solutions in a pair-feeding protocol for 5 days (5d). Metabolic acidosis developed within 24 h in NH(4)Cl-, but not in KCl-loaded rats. Interestingly, NH(4)Cl- but not KCl-loaded rats exhibited a significant natriuresis after 24 h of treatment. Urinary Na(+) excretion increased from 1.94 to 2.97 meq/24 h (P < 0.001) and returned to below baseline level (1.67 meq/l) after 5d of CMA. The protein abundance of the cortical Na-Cl cotransporter (NCC) remained unchanged at 24 h, but increased significantly (P < 0.01) after 5d of CMA. The protein abundance of alpha-, beta-, and gamma-subunits of the epithelial Na(+) channel (ENaC) in the cortex decreased sharply during the first 24 h and then returned to baseline levels after 5d of CMA. Interestingly, Sgk1 expression decreased after 24 h (-31%, P < 0.05) and then returned to baseline after 5d of CMA. Nedd4-2 expression was not altered during CMA. CMA enhanced serum aldosterone levels by 54% and increased the expression of aldosterone synthase in the adrenal gland by 134% after 5d of CMA. In conclusion, metabolic acidosis has dual effects on urinary Na(+) excretion. The early natriuresis results from decreased Na(+) reabsorption in the PT and Sgk1-related decreased ENaC activity in the DT and CD. Aldosterone-induced upregulation of NCC, Sgk1, and ENaC likely contributes to the antinatriuretic phase of metabolic acidosis. This adaptation prevents Na(+) wasting and volume depletion during chronic acid insult.
Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
Somia
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Faroqui
Sulaiman
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Sheriff
Hassane
H
Amlal
D000141:Acidosis, Renal Tubular / Q000139:chemically induced / Q000503:physiopathology*; D000450:Aldosterone / Q000097:blood; D000643:Ammonium Chloride / Q000009:adverse effects; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D002712:Chlorides / Q000097:blood; D003404:Creatinine / Q000652:urine; D004435:Eating / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000737:chemistry / Q000378:metabolism*; D000075702:Nedd4 Ubiquitin Protein Ligases; D010710:Phosphates / Q000097:blood; D011189:Potassium Chloride / Q000009:adverse effects; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine*; D015222:Sodium Channels / Q000032:analysis / Q000235:genetics / Q000502:physiology; D049992:Sodium Chloride Symporters / Q000032:analysis / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D000643:Ammonium Chloride; D001639:Bicarbonates; D001786:Blood Glucose; D002712:Chlorides; D003404:Creatinine; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; D010710:Phosphates; D011189:Potassium Chloride; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012964:Sodium; D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D044767:Ubiquitin-Protein Ligases; D000099184:Serum-Glucocorticoid Regulated Kinases; C000618479:NEDD4L protein, rat; C000618484:Nedd4 protein, rat