{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:32:43Z","timestamp":1768426363777,"version":"3.49.0"},"reference-count":37,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:p>Endothelin-1 inhibits collecting duct sodium reabsorption and stimulates proximal and distal tubule acidification in experimental animals both directly and indirectly via increased mineralocorticoid activity. Diet-induced acid loads have been shown to increase renal endothelin-1 activity, and it is hypothesized that increased dietary acid-induced endothelin-1 activity may be a causative progression factor in human renal insufficiency and that this might be reversed by provision of dietary alkali. We sought to clarify, in normal human volunteers, the role of endothelin-1 in renal acidification and to determine whether the effect is dependent on dietary sodium chloride. Acid-base equilibrium was studied in seven normal human volunteers with experimentally induced metabolic acidosis [NH<jats:sub>4<\/jats:sub>Cl 2.1 mmol\u00b7kg body weight (BW)<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>] with and without inhibition of endogenous endothelin-1 activity by the endothelin A\/B-receptor antagonist bosentan (125 BID p.o.\/day) both during dietary NaCl restriction (20 mmol\/day) and NaCl repletion (2 mmol NaCl\u00b7kg BW<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>). During NaCl restriction, but not in the NaCl replete state, bosentan significantly increased renal net acid excretion in association with stimulation of ammoniagenesis resulting in a significantly increased plasma bicarbonate concentration (19.0 \u00b1 0.8 to 20.1 \u00b1 0.9 mmol\/l) despite a decrease in mineralocorticoid activity and an increase in endogenous acid production. In pre-existing human metabolic acidosis, endothelin-1 activity worsens acidosis by decreasing the set-point for renal regulation of plasma bicarbonate concentration, but only when dietary NaCl provision is restricted.<\/jats:p>","DOI":"10.1152\/ajprenal.00309.2012","type":"journal-article","created":{"date-parts":[[2012,8,2]],"date-time":"2012-08-02T05:26:37Z","timestamp":1343885197000},"page":"F991-F999","source":"Crossref","is-referenced-by-count":10,"title":["Role of endothelin-1 in renal regulation of acid-base equilibrium in acidotic humans"],"prefix":"10.1152","volume":"303","author":[{"given":"Alexandra","family":"Pallini","sequence":"first","affiliation":[{"name":"University Department of Medicine, Kantonsspital Bruderholz, Bruderholz\/Basel, Switzerland; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry N.","family":"Hulter","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgen","family":"Muser","sequence":"additional","affiliation":[{"name":"University Department of Medicine, Kantonsspital Bruderholz, Bruderholz\/Basel, Switzerland; 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