The Mechanism of Suppression of Proximal Tubular Reabsorption by Saline Infusions*

Abstract

Summary. The mechanism by which expansion of extracellular fluid volume with isotonic saline suppresses reabsorption in the proximal tubule was studied in rats by examining the relations among glomerular filtration rate (GFR), absolute and fractional reabsorption of filtrate, intrinsic reabsorptive capacity (rate of reabsorption per unit tubular volume), transit time, and tubular volume.Saline infusions reduced the per cent of the glomerular filtrate reabsorbed in the proximal tubule from 50% during antidiuresis to 25% during saline diuresis. The suppression of proximal reabsorption was the result of two factors: 1) a 30% reduction of intrinsic reabsorptive capacity, and 2) a 26% reduction of tubular volume per unit GFR.GFR invariably rose during saline diuresis. However, prevention of the rise in GFR by aortic clamping had no effect on either the inhibition of intrinsic reabsorptive capacity or the reduction in tubular volume per unit GFR produced by saline infusions. Expansion of extracellular fluid volume with isotonic saline, therefore, depressed intrinsic reabsorptive capacity and tubular volume per unit GFR by some mechanism completely independent of GFR.The effects of furosemide administration were contrasted with those of saline infusions. Furosemide inhibited intrinsic reabsorptive capacity by 40% but had no significant effect on proximal fractional reabsorption. The failure to suppress fractional reabsorption was the consequence of a disproportionate rise in tubular volume (relative to GFR) that was sufficient to completely overcome the inhibition of intrinsic reabsorptive capacity. Inhibition of intrinsic reabsorptive capacity alone, therefore, will not result in a net suppression of reabsorption of filtrate in the proximal tubule. We concluded that, although intrinsic reabsorptive capacity was inhibited during saline diuresis, the critical factor responsible for translating this inhibition into effective net suppression of proximal reabsorption was the observed reduction in tubular volume per unit GFR. IntroductionThe diuresis induced by expanding extracellular fluid (ECF) volume with isotonic saline is due in part to a decrease in the fraction of the glomerular filtrate reabsorbed in the proximal convoluted tubule (1, 2). However, the mechanism by which saline infusions depress fractional reabsorption in the proximal tubule has not been examined.Previous studies in our laboratory (3, 4) explored the factors controlling fractional reabsorption in the proximal tubule under conditions in which glomerular filtration rate (GFR) was varied but ECF volume was kept constant. We found that the absolute rate of reabsorption during both aortic constriction and increased ureteral pressure was a direct function of tubular volume. When GFR was acutely reduced by constricting the aorta, tubular volume decreased proportionately to GFR; this resulted in a proportionate decrease in the reabsorptive rate, thereby maintaining constant fractional reabsorption. In contrast, when GFR was decreased by acutely elevating ur...

An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron

“…Rector, Sellman, Martinez-Maldonado, and Seldin observed a 40% inhibition of the intrinsic reabsorptive capacity of the proximal convoluted tubule in the rat after furosemide, as measured by the shrinking drop technique (7). Nevertheless, in agreement with the results in the dog (8) and monkey (6), they were unable to detect an inhibitory effect of the drug in the rat on fractional sodium reabsorption by the proximal tubule as measured in free flow studies.…”

Analysis of Direct Renal Actions of Alpha and Beta Adrenergic Stimulation Upon Sodium Excretion Compared to Acetylcholine

“…Watson (1966) concluded that all the increased sodium excreted could be accounted for by the decreased fractional reabsorption of sodium in the proximal tubule. The mechanism of this increased proximal tubular rejection of sodium as a result of saline loading is unknown (Rector, Sellman, Martinez-Maldonado & Seldin, 1967). The above evidence gives some basis for the validity of our use of the changes in tubular rejection fractions to explain the renal tubular effect of these drugs.…”

Effects of Acute Volume Expansion and Altered Hemodynamics on Renal Tubular Function in Chronic Caval Dogs

“…To the extent however, that the punctured segments identified by lissamine green do not represent a fixed anatomical portion of the entire proximal convolution, it is possible that small, but significant differences in fractional reabsorption of salt and water could be obscured by an unrecognized random pattern to the tubular punctures. Although no comparable data exist for the dog, Rector, Sellman, Martinez-Maldonado, and Seldin (20) have shown by micropuncture and microdissection techniques that the end-proximal tubule in rats as identified by lissamine green injections corresponds to 55-65% of the total length of the proximal tubule. If this were also the situation in dogs, then conclusions concerning fractional reabsorption in both groups of dogs are probably valid.…”