{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:44:26Z","timestamp":1790837066281,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T00:00:00Z","timestamp":1530576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1RO1\u2010DK099284"],"award-info":[{"award-number":["1RO1\u2010DK099284"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Dietary Na restriction, through the mineralocorticoid aldosterone, acts on epithelial Na channels via both fast (24\u00a0h) and slow (5\u20137\u00a0days) mechanisms in the kidney.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The fast effect entails increased proteolytic processing and trafficking of channel protein to the apical membrane. It is rapidly reversible by the mineralocorticoid receptor antagonist eplerenone and is largely lost when tubules are studied\n                            <jats:italic>ex vivo<\/jats:italic>\n                            .\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The slow effect does not require increased processing or surface expression, is refractory to acute eplerenone treatment, and is preserved\n                            <jats:italic>ex vivo<\/jats:italic>\n                            .\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Both slow and fast effects contribute to Na retention\n                            <jats:italic>in vivo<\/jats:italic>\n                            .\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Increased Na\n                            <jats:sup>+<\/jats:sup>\n                            reabsorption in the proximal tubule also promotes Na conservation under conditions of chronic dietary Na restriction, reducing Na\n                            <jats:sup>+<\/jats:sup>\n                            delivery to the distal nephron.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Changes in the activity of the epithelial Na channel (ENaC) help to conserve extracellular fluid volume. In rats fed a low\u2010salt diet, proteolytic processing of ENaC increased within 1\u00a0day, and was almost maximal after 3\u00a0days. The rapid increase in the abundance of cleaved \u03b1ENaC and \u03b3ENaC correlated with decreased urinary Na\n                      <jats:sup>+<\/jats:sup>\n                      excretion and with increased ENaC surface expression. By contrast, ENaC activity, measured\n                      <jats:italic>ex vivo<\/jats:italic>\n                      in isolated cortical collecting ducts, increased modestly after 3\u00a0days and required 5\u00a0days to reach maximal levels. The mineralocorticoid receptor antagonist eplerenone reversed the increase in cleaved \u03b3ENaC and induced natriuresis after 1 or 3\u00a0days but failed to alter either ENaC currents or Na\n                      <jats:sup>+<\/jats:sup>\n                      excretion after 7\u00a0days of Na restriction. We conclude that Na depletion, through aldosterone, stimulates ENaC via independent fast and slow mechanisms.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , amiloride\u2010induced natriuresis increased after 1\u00a0day of Na depletion. By contrast, hydrochlorothiazide (HCTZ)\u2010induced natriuresis decreased gradually over 7\u00a0days, consistent with increased ability of ENaC activity to compensate for decreased Na\n                      <jats:sup>+<\/jats:sup>\n                      reabsorption in the distal convoluted tubule. Administration of amiloride and HCTZ together increased Na\n                      <jats:sup>+<\/jats:sup>\n                      excretion less in Na\u2010depleted compared to control animals, indicating decreased delivery of Na\n                      <jats:sup>+<\/jats:sup>\n                      to the distal nephron when dietary Na is restricted. Measurements of creatinine and Li\n                      <jats:sup>+<\/jats:sup>\n                      clearances indicated that increased Na reabsorption by the proximal tubules is responsible for the decreased delivery. Thus, Na conservation during chronic dietary salt restriction entails enhanced transport by both proximal and distal nephron segments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp275988","type":"journal-article","created":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T05:27:46Z","timestamp":1525757266000},"page":"3585-3602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal Na\n                    <sup>+<\/sup>\n                    delivery"],"prefix":"10.1113","volume":"596","author":[{"given":"Gustavo","family":"Frindt","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Weill Cornell Medical College New York NY 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