Perturbation analysis of tubuloglomerular feedback in hydropenic and hemorrhaged rats

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Abstract
A closed-feedback-loop method was used to investigate regulation of SNGFR and distal fluid delivery by tubuloglomerular feedback (TGF) in hydropenic and hemorrhaged rats. Unblocked nephrons were perturbed by early proximal perfusion of previously collected, inulin-free, tubular fluid at 0, 7.5, and 15 nl/min, thereby increasing nephron fluid load. The resultant changes in SNGFR, tubular reabsorption, proximal intratubular pressure, and early distal flow were measured. During perfusion, SNGFR decreased and distal flow increased; the effect on reabsorption was variable. Analysis of the data indicated that the combined action of TGF and changes in proximal tubule and Henle's loop reabsorption were able to provide a maximum of 56% compensation for the effect of the perturbation on distal delivery in hydropenic rats and 70% compensation in hemorrhaged rats. In one group of hydropenic rats in which a significant fall in reabsorption was found, the total fluid load presented to the nephron, SNGFR plus the perfusion rate, was significantly better regulated than distal delivery. This result is consistent with the behavior of a model used to estimate the contribution of TGF to the observed regulation. The results indicated that TGF alone could provide 56% compensation for the perturbation in hydropenia and a significantly greater 72% compensation following hemorrhage. The conclusions are 1) that the properties of TGF are sufficient to result in significant regulation of distal fluid delivery and SNGFR, 2) that hemorrhage increases the strength of the TGF response, and 3) that TGF regulation of SNGFR and distal delivery is strongly influenced by changes in proximal tubule and loop of Henle reabsorption.

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