Potential natriuretic effects of limit-cycle oscillations mediated by tubuloglomerular feedback
Previously, we used a mathematical model to show that limit-cycle oscillations in nephron water and NaCl flow emerge when tubuloglomerular feedback (TGF) gain magnitude γ exceeds a critical value γc ≈ 3.5. Here, we used the model to investigate the effect of oscillations on the ability of TGF to regulate water and NaCl delivery to the distal nephron. For γ < γc, the TGF system, if transiently perturbed, returned to a steady-state in which distal delivery of water and NaCl was independent of γ. Moreover, feedback compensation for infinitesimal sustained perturbations agreed well with the predictions of linear systems theory (LST). However, for γ > γc, as the system tended to a limit cycle, two phenomena emerged. First, as γ increased from γc to 10, time-averaged NaCl delivery increased 3.7% above steady-state delivery, whereas water delivery deviated from the steady-state by < 0.5%. Second, for γ > γc, feedback compensation was reduced up to 21%, in comparison with the predictions of LST. Hence, these studies suggest that the emergence of TGF oscillations increases distal NaCl delivery and limits regulatory ability, effects that tend to enhance sodium excretion.
Layton, HE; Pitman, EB; Moore, LC
Volume / Issue
Start / End Page
International Standard Serial Number (ISSN)