A mathematical model of rat proximal tubule and loop of Henle (1137.9)

Abstract

PT and LOH 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 began with published models of superficial rat proximal convoluted tubule (PCT) (including flow‐dependent transport in a compliant tubule), and rat thick ascending Henle limb (AHL). This PCT was scaled down to represent outer medullary proximal straight tubule (PST), which was connected to thick AHL via a short descending limb. Superficial PT was scaled up to a juxtamedullary nephron, and connected to thick AHL via outer and inner medullary descending limbs, and inner medullary thin AHL. Medullary interstitial solute concentrations were specified. End‐tubule hydrostatic pressure was required to conform to a distal nephron flow resistance. The TGF signal was represented as a linear function of end‐AHL cytosolic Cl concentration. These two distal conditions required iterative solution of the model. Calculations revealed Na, K, and HCO3 reabsorption in all segments, with thin limb transport driven by the increases in lumen concentrations produced by osmotic water reabsorption. PST was a critical locus for NH4 secretion, due to high interstitial NH4, and cellular uptake via the Na,K‐ATPase. Late AHL cytosolic Cl was a sigmoidal function of flow, and appears suitable to represent the TGF signal.Grant Funding Source: Supported by NIH RO1‐DK29857