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HERO ID
2954530
Reference Type
Journal Article
Title
A mathematical model of rat proximal tubule and loop of Henle
Author(s)
Weinstein, AM
Year
2015
Is Peer Reviewed?
Yes
Journal
American Journal of Physiology: Renal Physiology
ISSN:
1931-857X
Volume
308
Issue
10
Page Numbers
F1076-F1097
PMID
25694479
DOI
10.1152/ajprenal.00504.2014
Web of Science Id
WOS:000354713000006
Abstract
Proximal tubule and loop of Henle function are coupled, with proximal transport determining loop fluid composition, and loop transport modulating glomerular filtration via tubuloglomerular feedback (TGF). To examine this interaction, we begin with published models of the superficial rat proximal convoluted tubule (PCT; including flow-dependent transport in a compliant tubule), and the rat thick ascending Henle limb (AHL). Transport parameters for this PCT are scaled down to represent the proximal straight tubule (PST), which is connected to the thick AHL via a short descending limb. Transport parameters for superficial PCT and PST are scaled up for a juxtamedullary nephron, and connected to AHL via outer and inner medullary descending limbs, and inner medullary thin AHL. Medullary interstitial solute concentrations are specified. End-AHL hydrostatic pressure is determined by distal nephron flow resistance, and the TGF signal is represented as a linear function of end-AHL cytosolic Cl concentration. These two distal conditions required iterative solution of the model. Model calculations capture inner medullary countercurrent flux of urea, and also suggest the presence of an outer medullary countercurrent flux of ammonia, with reabsorption in AHL and secretion in PST. For a realistically strong TGF signal, there is the expected homeostatic impact on distal flows, and in addition, a homeostatic effect on proximal tubule pressure. The model glycosuria threshold is compatible with rat data, and predicted glucose excretion with selective 1Na(+): 1glucose cotransporter (SGLT2) inhibition comports with observations in the mouse. Model calculations suggest that enhanced proximal tubule Na+ reabsorption during hyperglycemia is sufficient to activate TGF and contribute to diabetic hyperfiltration.
Keywords
glomerulotubular balance; tubuloglomerular feedback; ammonia; glucose; glomerular hyperfiltration
Tags
IRIS
•
Ammonia
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