Absolute Proximal Reabsorption Rate Research Articles

Renal haemodynamics, sodium and water reabsorption during continuous intravenous infusion of recombinant interleukin-2

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P=0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P=0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P=0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.

Renal haemodynamics, sodium and water reabsorption during continuous intravenous infusion of recombinant interleukin-2

1.Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma.2.Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18×106 i.u.·24 h-1·m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow.3.Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P = 0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P = 0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P = 0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1α increased by 98% (P = 0.022) and 175% (P = 0.022) respectively.4.The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.

Dopamine natriuresis in salt‐repleted, water‐loaded humans: a dose‐response study

Aims The purpose of the present study was to define the dose‐response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 μg kg−1 min−1 in normal volunteers. Methods While undergoing water diuresis, eight subjects were infused with 0, 1, 2, 3, 5, 7.5, 10 or 12.5 μg of dopamine kg−1 min−1 over 2 h in a randomized and double‐blind fashion. On each study day, renal clearance studies were performed during a 1 h baseline period and subsequently during the second 1 h infusion period. Lithium clearance (CLLi ) was used to estimate proximal tubular outflow. Results Cardiac output increased with the four highest doses. Mean arterial pressure followed a biphasic pattern with a decrease during the two lowest doses and a dose‐dependent increase from the 7.5 μg kg−1 min−1 dose onwards. Effective renal plasma flow increased with all doses of dopamine, but peaked with the 3 μg kg−1 min−1 infusion rate [ from 617 (585–649) ml min−1 with placebo to 915 (824–1006) ml min−1 (means with 95% CI, P<0.001)]. None of the doses changed glomerular filtration rate (GFR). Sodium clearance (CLNa ) and CLLi were elevated with the four lowest doses but increased further from 7.5 μg kg−1 min−1 onwards. Compared with placebo, the percentage increase in CLNa with increasing dose was 77 (5–159), 93 (13–172), 107 (24–190), 121 (60–181), 253 (65–441), 284 (74–494), and 212 (111–312) %, respectively. There were only small, inconsistent decreases in absolute proximal reabsorption rate (APR=GFR‐CLLi ). Fractional distal reabsorption of sodium (FDRNa=(CLLi‐CLNa )/CLLi ) decreased with all doses, reaching its nadir with 7.5 μg kg−1 min−1 [from 95.9 (94.6–97.2) % with placebo to 91.5 (90.0–93.0) % (P<0.01)] whereafter a flat dose‐response curve was observed. Conclusions In conclusion, the renal vasodilating effect of dopamine was maximal with 3 μg kg−1 min−1. The dose‐dependent attenuation seen with higher doses is consistent with an increased α‐adrenergic stimulation opposing the effect on dopaminergic receptors. The present CLLi studies confirm that dopamine increases proximal tubular outflow. The results suggest that the natriuretic effect of depressor doses of dopamine was primarily caused by attenuation of the increase in distal sodium reabsorption normally seen after an increase in proximal tubular outflow. Pressor doses further increased sodium excretion, indicating the presence of pressure natriuresis at these high doses.

On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption.

The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the absolute rate of proximal reabsorption (APR), causes a reduction in glomerular filtration rate (GFR), and activates the tubuloglomerular feedback mechanism (TGF) resulting in afferent vasoconstriction. The quantitative importance of the afferent vasoconstriction for the reduced GFR was tested by addition of a vasodilator during continuous infusion of ACZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ levels. Glomerular capillary pressure (Pgc) and proximal tubular pressure (Pprox) increased in parallel (by 3.1 and 3.0 mmHg, respectively) leaving pressure gradient (delta P) unchanged. APR, as estimated from the clearances of 51Cr-EDTA and lithium, remained unchanged. Urine flow almost doubled. GFR was only modestly reversed (pre-ACZ/ACZ/ACZ+dopamine: 100/77/83%). It is concluded that relieving the afferent vasoconstriction seen after carbonic anhydrase inhibition fails to restore GFR to its control value. This is due to the high flow resistance in the distal nephron segments during the increased tubular flow rates seen after ACZ. The high distal flow resistance causes a parallel change in Pgc and Pprox and thus leaves delta P nearly unchanged. The present study highlights the importance of the distal flow resistance in determining delta P and therefore GFR during conditions where tubular flow rate is increased.

Control of erythropoiesis in humans during prolonged exposure to the altitude of 6,542 m

Altitude hypoxia induces an increase in erythropoiesis. Some of the factors involved in the control of altitude polycythemia were studied. Ten subjects (4 women, 6 men) were exposed for 3 wk to extreme altitude (6,542 m). Blood was withdrawn in normoxia (N) and after 1 wk (H1), 2 wk (H2), or 3 wk (H3) at 6,542 m for the measurement of serum erythropoietin (EPO), blood hemoglobin (Hb), hematocrit (Hct), intraerythrocyte folate (Fol), and plasma ferritin (Fer) concentrations. Renal blood flow (RBF) and absolute proximal reabsorption rate (APR) were measured by the p-aminohippuric acid and lithium clearance, respectively, in N and H2 conditions. O2 supply to the kidneys was calculated using RBF and arterial O2 content (CaO2). After an initial sharp increase in EPO, it decreased at H2 and H3. Hct and Hb increased from N to H1 and H2 and then unexpectedly decreased from H2 to H3. Mean corpuscular Hb content (MCHC = Hb/Hct) was lower in all H than in N conditions. Increase in EPO at H1 varied from 3- to 134-fold among individuals. Women showed a smaller increase in Hct and Hb and a greater decrease in MCHC. Two women showed a large increase in EPO without increase in Hb. Fol was not modified by altitude hypoxia. Fer showed a marked decrease in H1 and H3 compared with N. Hb was positively related to Fer in hypoxia. Iron intake in food was markedly decreased during the 2-wk ascent to 6,542 m. EPO was inversely related to CaO2 and positively related to APR.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute hypoxia on renal and endocrine function at rest and during graded exercise in hydrated subjects.

Renal effects of altitude hypoxia are unclear. Renal and hormonal function was investigated in eight males at rest and during graded exercise at sea level (SL) and 48 h after rapid ascent to 4,350 m (HA). HA did not change resting values of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), sodium clearance (CNa), urine flow, or lithium clearance (CLi), which was used as an index of proximal tubular outflow. At rest, HA increased plasma norepinephrine concentration and decreased plasma concentrations of renin and aldosterone. Exercise decreased ERPF similarly in both environments. Normoxic exercise progressively reduced GFR, but at HA GFR only decreased during heavy exercise. This resulted in a higher filtration fraction during light and moderate hypoxic exercise. However, calculated absolute proximal reabsorption rate (GFR-CLi) at HA was higher during low-intensity exercise, and there were no significant differences between exercise-induced decreases in CLi, CNa, and urine flow at HA compared with SL. Exercise gradually increased plasma norepinephrine, but values were higher at HA during light and moderate exercise. The small changes in the renal response to low-intensity hypoxic exercise may be secondary to increased adrenosympathetic activity. However, antidiuretic and antinatriuretic effects of exercise were maintained in hypoxia and in both environments seemed to be the consequence of decreased proximal tubular outflow. The results demonstrate that renal glomerular and tubular function is well preserved in acute hypoxia despite marked hormonal changes.

Effects of hyperglycaemia on kidney function, atrial natriuretic factor and plasma renin in patients with insulin-dependent diabetes mellitus.

In normoalbuminuric patients with insulin-dependent diabetes mellitus, plasma atrial natriuretic factor (ANF), cyclic GMP and active renin and the renal clearances of [99Tcm]-diethylenetriaminepentaacetic acid (DTPA) lithium and sodium were studied on a hyperglycaemia day and a euglycaemia day. Baseline euglycaemia was achieved by an overnight variable insulin infusion, which during study days was fixed at the rate necessary to maintain euglycaemia in the morning. After a baseline euglycaemic clearance period of 90 min, measurements were repeated in a new 90-min period beginning 150 min later. On the hyperglycaemia day i.v. infusion of 20% glucose was started at the end of the euglycaemic baseline period, increasing blood glucose (5.3 +/- 1.3 vs 12.1 +/- 1.2 mmol l-1, p less than 0.01). On the euglycaemia day blood glucose declined (5.1 +/- 1.0 vs 4.2 +/- 1.0 mmol l-1, p less than 0.02). Glomerular filtration rate (GFR) was unchanged by acute hyperglycaemia (127 +/- 16 vs 129 +/- 24 ml min-1, NS), but nearly normalized during maintained euglycaemia on the euglycaemia day (124 +/- 17 vs 105 +/- 16 ml min-1, p less than 0.01). When comparing the hyperglycaemic study period with the similarly timed period on the euglycaemia day, GFR was elevated by hyperglycaemia (129 +/- 24 vs 105 +/- 16 ml min-1, p less than 0.01), while the renal clearances of lithium and sodium were similar. Consequently, the calculated absolute proximal reabsorption rate of sodium and water was elevated during hyperglycaemia. Hyperglycaemia reduced the slight decline in plasma concentrations of ANF and cyclic GMP observed on the euglycaemia day. Active renin, glucagon and plasma osmolality were unchanged. In conclusion, marked changes in glomerular filtration rate are induced by changes in blood glucose concentration, but the effect is delayed and thus not directly related to renal tubular transport of glucose. Hyperglycaemia does not affect renal clearances of lithium and sodium, while proximal tubular reabsorption is markedly stimulated. These changes are not related to changes in ANF, renin, glucagon or plasma osmolality.

Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules that is not fully compensated for in the distal tubules.

Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method.

The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 +/- 7%), sodium clearance (26 +/- 4%), lithium clearance (9 +/- 2%) and fractional lithium clearance (8 +/- 2%) was seen, as compared to the contralateral kidney with preserved innervation. Calculated absolute proximal reabsorption rate decreased significantly by 7 +/- 2%, while calculated absolute rates of distal reabsorption of sodium and water increased significantly by 9 +/- 2% and 8 +/- 2%. Low-frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 +/- 6%), sodium clearance (31 +/- 4%), lithium clearance (17 +/- 5%) and in fractional lithium clearance (18 +/- 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 +/- 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 +/- 5% and 16 +/- 5%. These changes in tubular sodium and water reabsorption during alterations in renal nerve activity occurred without measurable changes in renal blood flow (RBF) and glomerular filtration rate (GFR). Administration of amiloride had no significant effect either on the lithium clearance, RBF or GFR, while the sodium excretion rate increased and potassium excretion rate decreased, supporting that significant distal lithium reabsorption did not occur under the present experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic basis for the maintenance of glomerulotubular balance in young growing rats

AbstractPhysiologic basis for the maintenance of glomerulotubular balance in young growing rats. To examine the physiologic basis of preservation of glomerulotubular balance in young growing animals, we measured the various determinants for fluid transfer across the glomerular and postglomerular capillaries in young (∼40 days, N = 8) and adult (N = 8) male Munich-Wistar rats under mild volume expansion. The single nephron (SN) GFR increased by ∼2.5-fold from young to adult animals. The increase in SNGFR was due to marked rises in both glomerular plasma flow rate (QA) and ultrafiltration coefficient (Kf). The increase in QA was associated with a nearly 60% reduction in afferent and efferent arteriolar resistances. As with SNGFR, the absolute proximal reabsorption rate (APR) increased by some 2.5-fold, indicating preservation of perfect glomerulotubular balance. Of the factors determining peritubular capillary uptake of APR, the mean oncotic pressure difference across the peritubular capillary was similar in young and adult animals. The mean hydraulic pressure difference was also comparable in the two groups. By contrast, the peritubular capillary reabsorption coefficient (Kr) rose markedly and accounted entirely for the increase in peritubular capillary uptake of APR during growth. These results obtained under mild volume expansion indicate that the maintenance of glomerulotubular balance in the growing rat requires harmonious growth of renal microcirculation, that is, glomerular capillary (↑ Kf) and arteriolar (↑ QA) maturation balances the development of peritubular capillary (↑ Kr).Bases physiologiques du maintien de la balance glomérulotubulaire chez des rats jeunes en croissance. Afin d'examiner les bases physiologiques de la préservation de la balance glomérulotubulaire chez des animaux jeunes en croissance, nous avons mesuré les différents déterminants du transfert liquidien à travers les capillaires glomérulaires et postglomérulaires chez des rats mâles Munich-Wistar jeunes (∼40 jours, N = 8), et adultes (N = 8), au cours d'une expansion volémique modérée. La GFR néphronique individuelle (SN) s'est élevée de ∼2,5-fois des animaux jeunes aux animaux adultes. L'augmentation de SNGFR était due à des élévations marquées du débit plasmatique glomérulaire (QA) et du coefficient d'ultrafiltration (Kf). L'augmentation de QA était associée avec une réduction de presque 60% des résistances artériolaires afférentes et efférentes. De même que pour SNGFR, le débit absolu de réabsorption proximale (APR) s'est élevé de 2,5-fois, indiquant le maintien d'une balance glomérulotubulaire parfaite. Parmi les facteurs déterminant le passage capillaire péritubulaire d'APR, la différence de pression oncotique moyenne à travers le capillaire péritubulaire était identique chez les animaux jeunes et adultes. La différence de pression hydraulique moyenne était également comparable dans les deux groupes. En revanche, le coefficient de réabsorption capillaire péritubulaire (Kr) s'est élevé de façon marquée et était entièrement à l'origine de l'élévation du passage capillaire péritubulaire d'APR pendant la croissance. Ces résultats obtenus pendant une expansion volémique modérée indiquent que le maintien de la balance glomérulotubulaire chez le rat en croissance nécessite une croissance harmonieuse de la microcirculation rénale qu'est, la maturation du capillaire glomérulaire (↑ Kf) et artériolaire (↑ QA) équilibre le développement du capillaire péritubulaire (↑ Kr).

Effects of halothane-nitrous oxide inhalation anesthesia and Inactin on overall renal and tubular function in Sprague-Dawley and Wistar rats.

Real function, plasma renin concentration (PRC) and prostaglandin (PG) excretion rate was studied in groups of Sprague-Dawley (SPRD) and Wistar (WIST) rats anesthetized with either Halothane-N2O or Inactin. Conscious rats were used as controls. A. In Halothane-N2O anesthesia inulin clearance (CIN) and absolute proximal reabsorption rate (APR) was moderately decreased (by about 20%), while renal plasma flow (RPF), urine flow and solute excretion remained unchanged as compared to conscious rats. There was a linear relationship between the reciprocal of the proximal occlusion time (OT) and CIN in Halothane anesthesia indicating that the proximal luminal diameter was constant and independent of CIN. B. Inactin anesthesia CIN was similarly reduced but APR was more depressed (by about 35%). RPF and solute excretion rate decreased only in SPRD rats, while urine flow was significantly reduced in both strains. 1/OT was invariant to changes in CIN indicating luminal diameter variations in proportion to CIN. Urinary PGE2-and PGF2 alpha excretion rates and PRC were moderately elevated in operated animals of both strains regardless of the anesthetics used. It is concluded that renal functional parameters in surgically prepared rats are more severely depressed by Inactin than by Halothane-N2O anesthesia. The gas anesthesia is equally well tolerated by both strains of rats.

Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat.

Micropuncture study was performed in 21 mildly volume-expanded Munich-Wistar rats before and during partial aortic constriction to examine the effects of endogenous prostaglandins (PG) and angiotensin II (AII) on single nephron glomerular filtration rate (SNGFR) and absolute proximal reabsorption rate (APR). Animals received either vehicle (group 1), indomethacin (group 2), or indomethacin plus saralasin (group 3). Before aortic constriction, these inhibitors were without effect on values of SNGFR and APR. In group 1 rats, reduction in mean renal arterial perfusion pressure (RAP) to approximately 65 mm Hg resulted in marked and proportional declines in SNGFR and APR. With equivalent reduction in RAP in group 2 rats, however, SNGFR fell to a lesser extent and APR tended to increase slightly above preconstriction values. Indomethacin administration was therefore associated with disruption of glomerulotubular balance. In view of the roughly equivalent declines in afferent arteriolar resistance measured in groups 1 and 2, the magnitude of increase in efferent arteriolar resistance (R(E)) appeared to be of major importance in determining the observed presence or absence of glomerulotubular balance. Thus, the lesser fall in SNGFR in group 2 than in group 1 was a result of the higher value for glomerular capillary hydraulic pressure in group 2, a consequence of the higher value of R(E). The higher average value for APR during reduced RAP in group 2 than in group 1 is also attributable to this pronounced rise in R(E), the effect of which was to augment the net reabsorptive pressure both by favoring higher postglomerular oncotic pressure and lower downstream (peritubular capillary) hydraulic pressure. Since intrarenal release of AII is enhanced when RAP declines, and because AII is known to raise R(E) selectively, it is likely that endogenous AII brought about the marked increase in R(E) in group 2, which was readily demonstrable only in indomethacin-treated rats, presumably because endogenous PG synthesis was suppressed. In keeping with this conclusion, when the action of endogenous AII was inhibited by saralasin in group 3 rats, reduction in RAP failed to induce a rise in R(E), so that net filtration and reabsorption pressures again declined proportionally, as did SNGFR and APR. The present evidence therefore suggests that glomerulotubular balance is influenced to an important extent by the prevailing vasomotor tone of the efferent arteriole.

Peritubular capillary control of proximal tubule reabsorption in the rat

Changes in peritubular capillary hydrostatic and oncotic pressures, which probably affect net interstitial pressure and, thus, the force on fluid movement across the tubule basement membrane, can modulate absolute proximal reabsorption rate (APR). To examine the relationship between APR and net interstitial pressure, we measured peritubular capillary hydrostatic and oncotic pressure, single nephron filtration rate, APR, absolute distal reabsorption (ADR), and tubular hydrostatic pressure in hydropenic, saline-loaded, and plasma-loaded rats. Net interstitial pressure in saline loading was estimated from subcapsular hydrostatic pressure and lymph protein concentration measurements. The surface area-hydraulic conductivity product of the peritubular capillary network was estimated from these measurements with a model of capillary fluid exchange in which fluid uptake was defined to be APR plus ADR. The estimated value was assumed to remain constant in all three states, and was then used to estimate net interstitial pressure in hydropenic and plasma-loaded rats. APR and net interstitial pressure correlated strongly, a finding consistent with the hypothesized role for net interstitial pressure in regulating proximal reabsorption.

The effect on total renal and tubular function and plasma renin of a moderate isotonic saline load in rats anesthetized with amytal and inactin.

The renal effects of i.v. saline loading equal to 1% body weight (b.wt.) were studied in 2 groups of rats: group I was anesthetized with Amytal (15 mg/100 g b.wt. plus supplementary doses), group II with Inactin (12.5-15.0 mg/100 g b.wt.). In group I the saline load caused an increase in urine flow (+92%), solute excretion (+67%), inulin clearance (CIN) (+24%), PAH clearance (+31%) and absolute proximal reabsorption rate (+27%). Proximal fractional reabsorption and filtration fraction (FF) remained unchanged, while plasma oncotic pressure (COP) decreased by 10%. Plasma renin fell and there was an inverse relationship between renin concentration and proximal reabsorption rate. In group II urine flow and solute excretion increased after saline (+85% and 110%, respectively); CIN and absolute proximal reabsorption rate was lower than in group I and failed to increase after saline. Proximal fractional reabsorption was also lower and decreased after saline. COP as well as renin decreased as in group I, but no relationship between renin concentration and proximal reabsorption rate could be demonstrated. The data indicate that Inactin depresses both resting proximal tubular reabsorptive capacity and the tubular response to a physiological volume expansion. The results are compatible with the hypothesis that the renin-angiotensin system is significantly involved in regulation of proximal tubular function, while they are incompatible with the idea that peritubular COP plays any major role in this adjustment.