Papers Published
Abstract:
A simple mathematical model was used to investigate the spectral properties of the tubuloglomerular feedback (TGF) system. A perturbation, consisting of small-amplitude broadband forcing, was applied to simulated thick ascending limb (TAL) flow, and the resulting spectral response of the TGF pathway was assessed by computing a power spectrum from resulting TGF- regulated TAL flow. Power spectra were computed for both open- and closed- feedback-loop cases. Open-feedback-loop power spectra are consistent with a mathematical analysis that predicts a nodal pattern in TAL frequency response, with nodes corresponding to frequencies where oscillatory flow has a TAL transit time that equals the steady-state fluid transit time. Closed- feedback-loop spectra are dominated by the open-loop spectral response, provided that γ, the magnitude of feedback gain is less than the critical value γ(c) required for emergence of a sustained TGF-mediated oscillation. For γ exceeding γ(c), closed-loop spectra have peaks corresponding to the fundamental frequency of the TGF-mediated oscillation and its harmonics. The harmonics, expressed in a nonsinusoidal waveform for tubular flow, are introduced by nonlinear elements of the TGF pathway, notably TAL transit time and the TGF response curve. The effect of transit time on the flow waveform leads to crests that are broader than troughs and to an asymmetry in the magnitudes of increasing and decreasing slopes. For feedback gain magnitude that is sufficiently large, the TGF response curve tends to give a square waveshape to the waveform. Published waveforms and power spectra of in vivo TGF oscillations have features consistent with the predictions of this analysis.