Dependency of proximal tubular fluid transport on the load of glomerular filtrate

Abstract

In hydropenic rats, the reabsorption of glomerular filtrate by the proximal convoluted tubules was measured before and after reduction of its intratubular flow rate. Three different protocols were used. (1) In 26 tubules (14 rats), nephron glomerular filtration rate (SNGFR) was varied from 37.2 +/- 7.3 to 20.4 +/- 7.1 nl/min by microperfusing their loops of Henle at 0 to 5 nl/min and 40 nl/min, respectively. This 43% reduction of SNGFR was followed by a 36.0 +/- 23.3% reduction of volume reabsorption rate (P less than 0.001). Between both parameters a linear regression line can be calculated, which is given by y = 0.92 chi + 0.0017. (2) In 17 tubules (14 rats), SNGFR was altered again by feedback from 46.0 +/- 9.7 to 28.8 +/- 9.3 nl/min. The volume resorption from the first half of the proximal convoluted tubule was compared with the reabsorption in its late proximal segments, which were microperfused with proximal tubular fluid at a rate of 20 nl/min. The 36.8% reduction of SNGFR was followed by only a 28.2% reduction of volume reabsorption rate in the first half of the tubule. In the microperfused segments, however, reabsorption remained unaltered. (3) In 29 tubules (21 rats), at the midpoint of proximal convolutions, some of the tubule fluid was removed by a suction pump, and volume reabsorption rate in the late segments was compared with that in the early parts of this tubule, when SNGFR remained stable. The reduction of intratubular flow from 27.7 +/- 8.5 to 14.7 +/- 5.8 nl/min, which is 53% of control, were followed by a reduction of volume reabsorption rate in the late segment to 60.6% control. Between both parameters a regression line was calculated, which is given by y = 0.76 chi +/- 0.01. We conclude that the rate of volume reabsorption by the proximal tubule depends on its intratubular load of glomerular filtrate and, further, that this dependency accounts predominantly for the maintenance of glomerular tubular balance under conditions of hydropenia.

Glomerulotubular balance, dietary protein, and the renal response to glycine in diabetic rats

“…The present data complement prior evidence favoring a tubular hypothesis of glomerular hyperfiltration (18,21) according to which hyperfiltration originates with a reduced amount of salt reaching the macula densa. Furthermore, these data suggest that the tubular hypothesis might be extended to explain the salutary effects of dietary protein restriction on the diabetic kidney (6,22). In the present experiments, reducing dietary protein caused a primary decrease in tubular reabsorption and normalized the TGF signal.…”

Blood flow dependence of postglomerular fluid transfer and glomerulotubular balance.

“…SNGFR value thus calculated was 38.6 nl/min, SNGFR and APR. Since fluid load to the proximal tua value quite comparable to the observed value (45.2 nl/ bule is regarded, at least under certain circumstances min), indicating that even if a maximal increase in Kf oc- (41,42), to be important in modulating the rate of curred, it had little causal role in the increased SNGFR after reabsorption by the proximal tubule, we designed the plasma infusion. By contrast, when QA was assumed not to have increased with plasma infusion, SNGFR is predicted to second set of experiments aiming to increase EABF remain essentially at the hydropenic level (17.8 nl/min vs. while maintaining SNGFR constant.…”

Mechanosensory function of microvilli of the kidney proximal tubule

“…The experimental model has been the isolated perfused proximal tubule of the mouse, and our results are the first demonstration of flowdependence in the in vitro setting. The advantage of this preparation is not only the obvious constancy of the peritubular environment, but also elimination of the possibility of unspecified filterable factors that may modulate epithelial cell function (5). With the first description of the technique of in vitro perfusion, using proximal tubules from rabbit kidney, Burg and Orloff (20) had sought to reproduce the perfusion-absorption balance that had been observed in the intact rat kidney.…”

“…Because water reabsorption is driven by Na ϩ transport, a prerequisite for precise glomerulotubular balance is that luminal fluid flow modulates proximal tubule epithelial cell Na ϩ reabsorption. This flow effect has been termed ''perfusion-absorption balance'' (2,3) and has been demonstrated in microperfusion studies in rats (4)(5)(6)(7)(8). In mammalian kidneys, the primary pathway for proximal Na ϩ transport is into the cell through the Na ϩ -H ϩ exchanger isoform 3 (NHE-3) within the luminal cell membrane and out across the peritubular cell membrane via the Na ϩ , K ϩ -ATPase.…”