A closed-loop analysis of the tubuloglomerular feedback mechanism

The tubuloglomerular feedback (TGF) mechanism is of importance in the regulation of glomerular filtration rate (GFR). A second mechanism of potential importance is the change in proximal pressure caused by a change, for example, in the rate of proximal fluid reabsorption. The quantitative contributions of these two mechanisms to the regulation of GFR and the late proximal flow rate are not known. To determine the regulatory efficiency of these two mechanisms, the late proximal flow rate was perturbed by microperfusion with artificial tubular fluid in halothane-anesthetized Sprague-Dawley rats. The resulting changes in late proximal flow rate were measured by pulse injection of rhodamine dextran. Fluorescence was excited by means of a He-Ne laser. Bolus velocity was measured by videomicroscopy. Tubular pressure was measured by the servonulling method. The microperfusion rate was varied from -15 to 20 nl/min in steps of 5 nl/min. The open-loop gain (OLG) was 3.1 (range 1.5-9.9, n = 13) at the unperturbed tubular flow rate, and decreased as the tubular flow rate was either increased or decreased. The proximal pressure increased by 0.21 +/- 0.03 mmHg per unit increase in late proximal flow rate (nl/min). By use of a mathematical model of the glomerulus, it is estimated that under the present experimental conditions the pressure increase contributes 8% (range 3-15%) of the OLG. It is concluded that, for small perturbations around the operating point, TGF accounts for most of the regulation of GFR and the late proximal flow rate, with changes in the proximal pressure of lesser importance. Furthermore, under closed-loop conditions the operating point for the TGF mechanism is at or close to the point of maximal sensitivity.