Sex differences in solute transport along the nephrons: effects of Na + transport inhibition
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 + transporters and channels. The goal of the present study was to investigate the...
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Published in | American journal of physiology. Renal physiology Vol. 319; no. 3; pp. F487 - F505 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Physiological Society
01.09.2020
|
Series | Sex and Gender in Renal Health and Function |
Online Access | Get full text |
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Summary: | 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
+
transporters and channels. The goal of the present study was to investigate the extent to which inhibitors of transepithelial Na
+
transport (T
Na
) 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
+
/H
+
exchanger 3 (NHE3), bumetanide-sensitive Na
+
-K
+
-2Cl
−
cotransporter (NKCC2), Na
+
-Cl
−
cotransporter (NCC), and amiloride-sensitive epithelial Na
+
channel (ENaC). NHE3 inhibition simulations predicted a substantially reduced proximal tubule T
Na
, and NKCC2 inhibition substantially reduced thick ascending limb T
Na
. 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
Na
, it nonetheless had a notable effect of enhancing excretion of Na
+
, K
+
, and Cl
−
, particularly in female rats. Inhibition of ENaC was predicted to have opposite effects on the excretion of Na
+
(increased) and K
+
(decreased) and to have only a minor impact on whole kidney T
Na
. 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
+
and K
+
excretion in response to diuretics and Na
+
transporter mutations. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1931-857X 1522-1466 |
DOI: | 10.1152/ajprenal.00240.2020 |