{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:47:38Z","timestamp":1778276858916,"version":"3.51.4"},"reference-count":38,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:p>Chronic metabolic acidosis (CMA) is associated with decreased NaCl reabsorption in the proximal tubule (PT). However, the effect of CMA on Na<jats:sup>+<\/jats:sup>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<jats:sub>4<\/jats:sub>Cl, or 0.28 M KCl solutions in a pair-feeding protocol for 5 days (5d). Metabolic acidosis developed within 24 h in NH<jats:sub>4<\/jats:sub>Cl-, but not in KCl-loaded rats. Interestingly, NH<jats:sub>4<\/jats:sub>Cl- but not KCl-loaded rats exhibited a significant natriuresis after 24 h of treatment. Urinary Na<jats:sup>+<\/jats:sup>excretion increased from 1.94 to 2.97 meq\/24 h ( P &lt; 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 &lt; 0.01) after 5d of CMA. The protein abundance of \u03b1-, \u03b2-, and \u03b3-subunits of the epithelial Na<jats:sup>+<\/jats:sup>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 (\u221231%, P &lt; 0.05) and then returned to baseline after 5d of CMA. Nedd4\u20132 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<jats:sup>+<\/jats:sup>excretion. The early natriuresis results from decreased Na<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>wasting and volume depletion during chronic acid insult.<\/jats:p>","DOI":"10.1152\/ajprenal.00338.2005","type":"journal-article","created":{"date-parts":[[2006,2,23]],"date-time":"2006-02-23T01:12:43Z","timestamp":1140657163000},"page":"F322-F331","source":"Crossref","is-referenced-by-count":27,"title":["Metabolic acidosis has dual effects on sodium handling by rat kidney"],"prefix":"10.1152","volume":"291","author":[{"given":"Somia","family":"Faroqui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sulaiman","family":"Sheriff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassane","family":"Amlal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1996.271.4.F917"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00901.x"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.1.C126"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00394.2003"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.50.33681"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1993.264.6.F1027"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Chomczynski Pand Sacchi N.Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal Biochem162: 156\u2013159, 1987.","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.7.1991"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-001-0098-x"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.1.F46"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1988.139"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1042\/bj20021375"},{"key":"R13","unstructured":"Hamm LLand Alpern RJ.Physiology and pathophysiology. 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