Feedback-mediated dynamics in a model of coupled nephrons with compliant thick ascending limbs.
The tubuloglomerular feedback (TGF) system in the kidney, a key regulator of glomerular filtration rate, has been shown in physiologic experiments in rats to mediate oscillations in thick ascending limb (TAL) tubular fluid pressure, flow, and NaCl concentration. In spontaneously hypertensive rats, TGF-mediated flow oscillations may be highly irregular. We conducted a bifurcation analysis of a mathematical model of nephrons that are coupled through their TGF systems; the TALs of these nephrons are assumed to have compliant tubular walls. A characteristic equation was derived for a model of two coupled nephrons. Analysis of that characteristic equation has revealed a number of parameter regions having the potential for differing stable dynamic states. Numerical solutions of the full equations for two model nephrons exhibit a variety of behaviors in these regions. Also, model results suggest that the stability of the TGF system is reduced by the compliance of TAL walls and by internephron coupling; as a result, the likelihood of the emergence of sustained oscillations in tubular fluid pressure and flow is increased. Based on information provided by the characteristic equation, we identified parameters with which the model predicts irregular tubular flow oscillations that exhibit a degree of complexity that may help explain the emergence of irregular oscillations in spontaneously hypertensive rats.
Layton, AT; Bowen, M; Wen, A; Layton, HE
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