{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:46:49Z","timestamp":1788169609549,"version":"build-2803163510"},"reference-count":27,"publisher":"American Physiological Society","issue":"2","funder":[{"name":"Danish Medical Reseach Council","award":["12-127174"],"award-info":[{"award-number":["12-127174"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2015,7,15]]},"abstract":"<jats:p>The loop diuretic furosemide inhibits NaCl reabsorption in the thick ascending limb (TAL). In addition, furosemide acidifies the urine, which is traditionally explained by increased Na<jats:sup>+<\/jats:sup>loading to the distal tubule causing an activation of H<jats:sup>+<\/jats:sup>secretion via H<jats:sup>+<\/jats:sup>-ATPase in \u03b1-intercalated cells. The inability to acidify urine in response to furosemide serves to diagnose distal renal tubular acidosis (dysfunction of \u03b1-intercalated cells). Since the TAL is important for acid\/base regulation, we speculated that it is involved in furosemide-induced urinary acidification. Luminal furosemide (100 \u03bcM) caused major, stable, and reversible intracellular alkalization (7.27 \u00b1 0.06 to 7.6 \u00b1 0.04) in isolated perfused murine medullary TAL and pronounced H<jats:sup>+<\/jats:sup>secretion. This H<jats:sup>+<\/jats:sup>secretion was fully inhibited with luminal amiloride (1 mM) and the Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchanger (NHE)3-specific antagonist #4167 (1 \u03bcM). Moreover, furosemide triggered a substantial drop of intracellular Na<jats:sup>+<\/jats:sup>concentration in the medullary TAL. These results suggest that the furosemide-induced H<jats:sup>+<\/jats:sup>secretion is a consequence of a drop in intracellular Na<jats:sup>+<\/jats:sup>concentration, increasing the driving force for NHE3. Intriguingly, in whole animal experiments, furosemide-induced urinary acidification and net acid excretion were markedly reduced by specific NHE3 inhibition. Furthermore, the furosemide-induced urinary acidification was partially preserved during epithelial Na<jats:sup>+<\/jats:sup>channel inhibition with benzamil. These results provide new insights in the mechanism of furosemide-induced urinary acidification and emphasize the role of the TAL in renal acid\/base handling.<\/jats:p>","DOI":"10.1152\/ajprenal.00154.2015","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T01:32:18Z","timestamp":1432171938000},"page":"F146-F153","source":"Crossref","is-referenced-by-count":47,"title":["Furosemide-induced urinary acidification is caused by pronounced H<sup>+<\/sup>secretion in the thick ascending limb"],"prefix":"10.1152","volume":"309","author":[{"given":"Pauline I. 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