Limit-cycle oscillations and tubuloglomerular feedback regulation of distal sodium delivery

Abstract

A mathematical model was used to evaluate the potential effects of limit-cycle oscillations (LCO) on tubuloglomerular feedback (TGF) regulation of fluid and sodium delivery to the distal tubule. In accordance with linear systems theory, simulations of steady-state responses to infinitesimal perturbations in single-nephron glomerular filtration rate (SNGFR) show that TGF regulatory ability (assessed as TGF compensation) increases with TGF gain magnitude γ when γ is less than the critical value γc, the value at which LCO emerge in tubular fluid flow and NaCl concentration at the macula densa. When γ > γc and LCO are present, TGF compensation is reduced for both infinitesimal and finite perturbations in SNGFR, relative to the compensation that could be achieved in the absence of LCO. Maximal TGF compensation occurs when γ ≈ γc. Even in the absence of perturbations, LCO increase time-averaged sodium delivery to the distal tubule, while fluid delivery is little changed. These effects of LCO are consequences of nonlinear elements in the TGF system. Because increased distal sodium delivery may increase the rate of sodium excretion, these simulations suggest that LCO enhance sodium excretion.