Mechanism of glomerulotubular balance. II. Regulation of proximal tubular reabsorption by tubular volume, as studied by stopped-flow microperfusion.

Abstract

Recent micropuncture studies (1-3) have shown that reductions in glomerular filtration rate (GFR) induced by aortic constriction are accompanied by proportionate changes in the rate of proximal tubular reabsorption, thus maintaining constant fractional reabsorption (i.e., glomerulotubular balance). We have shown, however, that similar reductions in GFR, induced by elevating ureteral pressure, are associated with increased fractional reabsorption in the proximal convoluted tubule (3). An analysis of the effects of aortic constriction and increased ureteral pressure on the relations among GFR, fractional reabsorption, tubular velocity, and tubular size led to the conclusion that tubular volume was the critical factor governing the proximal reabsorptive rate (3).In our previous studies, however, tubular volume and reabsorptive rate were estimated indirectly from an analysis of tubular fluid to plasma ratios of inulin [(TF/P)In] and the transit time. The present experiments were designed to investigate in a more direct fashion the effects of altering tubular dimensions on the intrinsic reabsorptive capacity of the tubular epithelium. The stoppedflow microperfusion technique of Gertz (4), in which the rate of reabsorption of a drop of isotonic saline placed between two columns of oil in an isolated segment of the tubule is measured, was used * Submitted for publication August 25, 1965; accepted December 27, 1965. This work was supported in part by a grant from the Dallas Heart Association and in part by training grant 5 TI HE 5469-04 from the National Institutes of Health, U. S. Public Health Service. to estimate the intrinsic reabsorptive capacity of the tubular epithelium. This method has the great advantage of permitting an assessment of tubular reabsorption independent of glomerular filtration and velocity flow.In the first series of experiments the effect of renal hypoperfusion, induced by constriction of the aorta above the renal arteries, on the rate of proximal reabsorption was examined. In the second series of experiments the role of tubular geometry in glomerulotubular balance was evaluated more precisely by measuring the rate of tubular reabsorption before and after dilatation of the proximal tubules. Graded dilatation was achieved by applying hydrostatic pressure to the renal pelvis. In a third series of experiments, increased ureteral pressure was superimposed on aortic constriction to exclude the possibility that the experimental procedure per se rather than tubular size was determining reabsorption.

Effect of changes in renal perfusion pressure on the suppression of proximal tubular sodium reabsorption due to saline loading

“…Thus, when perfusion pressure was lowered to the range of 70-90 mm Hg in saline-loaded rats, the reabsorptive ti of a column of isotonic NaC1 injected into the proximal tubule was only moderately prolonged in some animals and in others (rat Nos. 2, 4, 7, and 10) was entirely within the range found by others in nondiuretic rats (9,10,18,19,27). The over-all mean for C/irr' during the first constriction period (0.063/sec), calculated from equation 1, is very similar to that reported by Brenner, Bennett, and Berliner (23) for nondiuretic rats (0.062/ sec).…”

“…The rise in GFR which often occurs in the rat during saline loading would thus not be accompanied by a proportionate increase in the volume of the proximal tubule. According to the tubular geometry hypothesis of regulation of sodium transport (9,19,27,30), a decrease in the ratio 7rr2d/Vo could contribute to a fall in fractional reabsorption of sodium and water in the proximal tubule. The present observations are compatible with the view that a change in peritubular physical forces is responsible for the decrease in 7rr2d/Vo which normally occurs during a saline diuresis, since when renal perfusion pressure was reduced acutely by aortic constriction, this ratio remained within the normal or even highnormal range (9,11).…”

Mechanism of glomerulotubular balance. I. Effect of aortic constriction and elevated ureteropelvic pressure on glomerular filtration rate, fractional reabsorption, transit time, and tubular size in the proximal tubule of the rat.

“…As pointed out by -Gottschalk (17), the currently available micropuncture data that relate fractional reabsorption to distance along the proximal tubule are not sufficiently precise to permit a choice between these two models. Gertz (13), however, found that C/7rr2 measured by the shrinking-drop technique is the same in different portions of the proximal convolution; we have confirmed this finding (18). Since 7rr2 in the shrinking-drop technique is independent of tubular location, the constancy of the expression C/7rr2 suggests that the intrinsic reabsorptive properties of the proximal convoluted tubule are uniform along its length.…”

“…It should be noted that in the experiments of Gertz and his associates the rats were not given adequate amounts of saline to replace surgical losses, so that the kidneys were functioning against the background of reduced effective ECF volume. We (18) have also observed that acutely lowering GFR in antidiuretic rats that are not given saline to replace surgical losses of extracellular fluid results in increased transit time and elevation of the calculated (TF/P)in ratio; if, however, the rats are given sufficient saline to correct for surgical losses, but not enough to induce saline diuresis, transit time remains constant when GFR is reduced. Although the results obtained by Gertz and his colleagues and by us in nonsaline-repleted rats appear to be in disagreement with the results obtained in the present studies with rats undergoing saline diuresis, all of the studies are in complete agreement that (TF/P) i is related to transit time (T) by the expression, In (TF/P) i.…”

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

“…to a large extent, inferential evidence, it has been widely held until recently that the cross-sectional area of the lumen of the proximal tubule is the principal determinant of the rate of sodium reabsorption by this segment (19)(20)(21)(22). More recent studies in the rat (11,23) and rabbit (24) have provided information that strongly opposes this interpretation.…”