Dynamics of tubuloglomerular feedback adaptation to acute and chronic changes in body fluid volume

Abstract

Experiments were performed in anesthetized rats to investigate the time course of the adaptive changes in tubuloglomerular feedback reactivity and juxtaglomerular renin activity induced by DOCA and NaCl loading (isotonic saline as drinking fluid plus daily injections of 25 mg/kg DOCA). In these DOCA escaped rats we studied further the effect of acute volume depletion and repletion on the magnitude of feedback responses. A significant reduction of feedback reactivity was found on the fifth day after starting the DOCA-salt treatment with maximum depression being established after two weeks. In contrast, significant reduction of juxtaglomerular renin content required 10 days and maximum depression three weeks of DOCA-salt administration. In DOCA-salt treated animals with severely curtailed feedback responses acute volume depletion was induced by a single injection of furosemide (10 mg/kg) leading to an excretion of 0.49 ±0.17 mEq sodium and a mean decrease of body weight of 2.17±0.22% over a period of 60–70 min. Mean feedback response (expressed as percent change of early proximal flow rate caused by elevating loop of Henle flow rate from zero to 40 nl/min) was −43.9 ±4.0%, significantly greater than in the pre-depletion phase and indistinguishable from responses seen in normal control rats. Repletion of extracellular volume by infusing HCO₃-Ringer solution over 20 min induced a reduction in feedback responsivity to −12.0±2.9%. Plasma and juxtaglomerular renin concentration increased with volume depletion and decreased with volume repletion, but remained considerably lower than observed in normal control rats. Our results suggest that the tubuloglomerular feedback system responds to acute alterations in extracellular volume with rapid adaptations in its reactivity which is consistent with its role in the control of sodium excretion.