Old and New Methods to Study Tubuloglomerular Feedback
Friday, February 12, 1999 - 11:15am - 12:00pm
Scott Thomson (University of California, San Diego)
Tubuloglomerular feedback (TGF) is usually studied in rats by open-loop micropuncture. In such experiments flow in the tubule is interrupted, the loop of Henle is perfused with a pump, and the behavior of TGF response is quantified by correlating glomerular capillary pressure (PGC) or nephron GFR (SNGFR) with the pump rate. There are two main reasons why such data may yield false predictions as to how well TGF actually stabilizes nephron function. First, changes in PGC are not required in order for SNGFR to change; Second, the TGF response is non-linear and saturable such that the behavior of the system will depend on the which region of the TGF curve the natural operating point happens to reside. However, the natural operating point of a nephron is rendered indeterminate during open-loop micropuncture. Within the past decade it has become possible to measure flow in the proximal tubule without interrupting that flow. Thus it has become possible to study TGF by closed-loop analysis in which the nephron is perturbed in known reference to its natural operating point by adding or subtracting fluid in the free-flowing late proximal tubule while flow is monitored at a site immediately upstream. The changes in tubular flow corresponding to a set of perturbations can be used to predict the homeostatic efficiency of TGF. Several indices of TGF efficiency have been employed, but each of these is a discreet monotonic function of the product of the slope of the TGF curve and the slope of a curve which describes the feed-forward dependence of flow in the tubule on SNGFR. Through this approach it has been demonstrated that TGF compensates for small perturbations in ambient flow with 60-75% efficiency, that TGF resets to optimize its own efficiency, and that the specific vascular elements which mediate the TGF response differ depending on whether the nephron is responding to a positive or negative perturbation.