{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:47:59Z","timestamp":1787017679572,"version":"build-2736575974"},"reference-count":96,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["2R01DK083785"],"award-info":[{"award-number":["2R01DK083785"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada 150 Research Chair"},{"name":"NSERC Discovery Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:p>\n                    Each day, ~1.7 kg of NaCl and 180 liters of water are reabsorbed by nephron segments in humans, with urinary excretion fine tuned to meet homeostatic requirements. These tasks are coordinated by a spectrum of renal Na\n                    <jats:sup>+<\/jats:sup>\n                    transporters and channels. The goal of the present study was to investigate the extent to which inhibitors of transepithelial Na\n                    <jats:sup>+<\/jats:sup>\n                    transport (T\n                    <jats:sub>Na<\/jats:sub>\n                    ) along the nephron alter urinary solute excretion and how those effects may vary between male and female subjects. To accomplish that goal, we developed sex-specific multinephron models that represent detailed transcellular and paracellular transport processes along the nephrons of male and female rat kidneys. We simulated inhibition of Na\n                    <jats:sup>+<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    exchanger 3 (NHE3), bumetanide-sensitive Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -2Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter (NKCC2), Na\n                    <jats:sup>+<\/jats:sup>\n                    -Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter (NCC), and amiloride-sensitive epithelial Na\n                    <jats:sup>+<\/jats:sup>\n                    channel (ENaC). NHE3 inhibition simulations predicted a substantially reduced proximal tubule T\n                    <jats:sub>Na<\/jats:sub>\n                    , and NKCC2 inhibition substantially reduced thick ascending limb T\n                    <jats:sub>Na<\/jats:sub>\n                    . Both gave rise to diuresis, natriuresis, and kaliuresis, with those effects stronger in female rats. While NCC inhibition was predicted to have only minor impact on renal T\n                    <jats:sub>Na<\/jats:sub>\n                    , it nonetheless had a notable effect of enhancing excretion of Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    , and Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    , particularly in female rats. Inhibition of ENaC was predicted to have opposite effects on the excretion of Na\n                    <jats:sup>+<\/jats:sup>\n                    (increased) and K\n                    <jats:sup>+<\/jats:sup>\n                    (decreased) and to have only a minor impact on whole kidney T\n                    <jats:sub>Na<\/jats:sub>\n                    . Unlike inhibition of other transporters, ENaC inhibition induced stronger natriuresis and diuresis in male rats than female rats. Overall, model predictions agreed well with measured changes in Na\n                    <jats:sup>+<\/jats:sup>\n                    and K\n                    <jats:sup>+<\/jats:sup>\n                    excretion in response to diuretics and Na\n                    <jats:sup>+<\/jats:sup>\n                    transporter mutations.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00240.2020","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T05:19:04Z","timestamp":1596431944000},"page":"F487-F505","source":"Crossref","is-referenced-by-count":73,"title":["Sex differences in solute transport along the nephrons: effects of Na\n                    <sup>+<\/sup>\n                    transport inhibition"],"prefix":"10.1152","volume":"319","author":[{"given":"Rui","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, 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