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The transition between the glomerulus and the proximal tubule was studied by light and electron microscopy in perfusion-fixed rabbit kidneys. In most nephrons a transitional segment of tubule occurred between the Bowman's capsule and the proximal tubule proper. This initial part of the tubule was lined by flattened cells and formed a cytologically distinct neck segment. The nephron population was heterogeneous with respect to the length of this neck segment regardless of the level of the cortex. The neck cells contained an abundance of thin filaments often oriented at right angles to the long axis of the tubule and comparable in thickness to actin filaments. The presence of actin-like filaments suggests that neck cells may effect changes in the diameter of the neck segment and, thus, influence single nephron glomerular filtration rate.

Cellular autophagy in convoluted tubules of kidney was studied in 24 rats, killed in pairs at constant time intervals during one diurnal cycle, by (a) morphometric evaluation of tubular cells by the point-counting method in randomly sampled micrographs, and (b) selective search for autophagic vacuoles (AV) directly on the electron microscopy screen. The total area of tubular cells recorded in the electron microscopy sections was 93 X 10(-4) mum2. Since the distal convoluted tubules, covering about 12% of the whole tubulocellular area, contained only 3-4% of all AV, they were omitted from the main calculations. The number of AV per area unit and the total amount of segregated material showed a distinct diurnal rhythm, synchronous for the different types of AV which were distinguished from each other according to their contents. The minimum was found during the night, the maximum during the day. This rhythm appears similar to that described elsewhere in liver cells. The mean segregated fractions were calculated from the relation of segregated to nonsegregated material in proximal convoluted tubular cells. The segregated fraction of the mitochondria was 4.4 X 10(-4). This value could account for the degradation of all mitochondria in a cell within 15 days, i.e., the upper limit of the lifetime of mitochondrial DNA in the cortex of the kidney, if one assumes that a mitochondrion is destroyed within 10 min after being segregated. The degregated fraction of microbodies was 11.7 X 10(-4). This suggests a shorter lifetime of these organelles. It is concluded that cellular autophagy plays a significant role in the turnover of cytoplasmic constituents, including the membranes of the endoplasmic reticulum.

14C-labeled angiotensin II ([14C]AII) and tritiated inulin ([3H]In) were infused into individual nephrons in Inactin-anesthetized rats and urinary excretion was measured. Site of infusion was identified by neoprene injection and microdissection. In other experiments with higher doses of [14C]AII, microperfused at 10-4-10-5 M (concentrations 10-5-10-6 higher than contained in plasma), [14C]AII and its urinary metabolites were identified and quantified by two-dimensional peptide mapping. Recovery of 14C was 10.9% when proximal tubules were infused and 94.8% when distal tubules were infused. There was no correlation with tubular length in either case. For proximal tubules, two-thirds of the 11% recovered from urine appeared as peptide fragments of AII. With distal tubules almost all 14C activity appeared as intact AII. The principal metabolic product recovered from urine after proximal injection was the chymotryptic peptide, and its recovery was inversely related to tubular length. It is suggested that rapid removal of [14C]AII by proximal tubular cells occurs by enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder

The hydraulic conductivity of the rat proximal tubular wall was determined using colloidal solutions perfused in short (50--200 mum) (SMP) or long (90--200 mum) (LMP) proximal tubular segments. In SMP human serum albumin (HSA) or polyvinylpyrrolidone (PVP) was added to raffinose solutions. A Lp of 0.019 nl-min-1-mm-1-mm Hg-1 was found when high colloid concentrations were used while values of 0.055--0.092 were found when low colloid concentrations were used. In other experiments, the Lp was determined by perfusing short tubular segments with pure raffinose solutions. A value of 0.015 nl-min-1-mm-1-mm Hg-1 was found. This is twice the value found when raffinose solutions were perfused through long tubular segments and it is concluded that the short microperfusion technique overestimates Lp with a factor of two. When microperfusions of long tubular segments were conducted, PVP was added to an equilibrium solution consisting of NaCl (110 mM) and raffinose (80 mM). Lp was found to be 0.018--0.021 when high colloid concentrations were used, while a value of 0.029 was found when a low colloid concentration was used. As found in both SMP and LMP a decrease in Lp's with increasing colloid concentrations indicates that a significant influence of radial concentration differences is highly probable. It is therefore suggested that the highest Lp derived when using the lowest colloid concentrations represents the best estimate. With this Lp value (0.03--0.05 nl-min-1-mm-1-mm Hg-1) and the existing transtubular hydrostatic and oncotic pressure difference it can be calculated that these passive forces might constitute the driving force for 1/3 of the fluid reabsorbed in the proximal tubule.

Autoregulation of glomerular filtration rate (GFR) was examined during uteral orarterial constriction in anesthetized dogs after renal denervation. GFR was sustaineduntil ureteral pressure greater than 80 mmHg, provided renal arterial pressure exceeded 180 mmHg, but fell at ureteral pressure less than 54 mmHg when arterial pressure averaged 127 plus or minus 5 mmHg; renal blood rose as GFR declined. Ethacrynic acid, saline, or mannitol infusion increased tubular pressure without reducing GFR,but during subsequent ureteral constriction GFR fell at uteral pressure less than 40mmHg. During arterial constriction GFR was maintained at lower arterial pressures in hydropenic than in diuretic dogs. Because of thisdifference in the range of autoregulation, saline infusion increased GFR more in hydropenic than in diuretic dogs except at high arterial pressure. This response to reduced plasma oncotic pressure and the constancy of GFR over a wide range of proximal tubular and arterial pressure indicate constancy of thehydrostatic transmural pressure of glomerular capillaries. Afferent arteriolar resistance is, in addition to a regulation by transmural pressure, perhaps controlled by vascular stretch receptors in the glomeruli.

Hydrostatic pressures were measured in cortical tubules, long loops of Henle, terminal collecting ducts, and in vasa recta in hamsters. In hydropenia, the loops of Henle and terminal collecting ducts provided the major fluid flow resistances, as judged by the location of hydrostatic pressure drops. In mannitol or saline diuresis, hydrostatic pressures in all tubular segments increased, but pressure drops in loops of Henle disappeared, indicating dilatation of loops. The major pressure drop was in terminal collecting ducts, especially in ducts of Bellini, even though these tubular segments also dilated. At highest urine flows, cortical tubule pressures were higher with the ureter and renal pelvis intact than when they were excised, suggesting laminar flow in the ureter adds a flow resistance at high flows. The pressure drop across the medullary capillary bed was 1-2 mmHg. The summation of medullary capillary hydrostatic and colloid osmotic pressures favored fluid uptake from the interstitium, a relationship enhanced by vasa recta geometry which ensures that descending vasa recta offer 4 times the flow resistance of ascending vessels.

In this review current hypotheses for the regulation of filtration rate and the subsequent reabsorption of that filtrate by the proximal tubule are discussed. In the rat the filtration rate is highly plasma flow dependent because of the phenomenon of filtration equilibrium. On the other hand, in man and dog filtration rate is much less dependent on renal plasma flow. In these species glomerular capillary pressure rather than glomerular plasma flow may be the primary determinant of filtration. Three hypotheses for the autoregulation of glomerular filtration are discussed. Of these the myogenic theory, which holds that increases in perfusion pressure result in an intrinsic contraction of the smooth muscle in the walls of the afferent arterioles, remains the best, if not completely adequate, explanation for the phenomenon. The role of a macula densa feedback mechanism is controversial, although data are presented which strongly militate against this hypothesis. Similarly, the prostaglandins, although important in determining vascular resistance, probably do not mediate autoregulation. Two prevalent hypotheses for the regulation of fluid reabsorption by the proximal tubule, the physical factor hypothesis and the humoral hypothesis, are discussed. Data presented indicate that peritubule Starling forces have a marked effect on isotonic reabsorption by the proximal tubule in the presence of volume expansion and enhanced backleak into the proximal tubule lumen. However, in hydropenia and diminished backleak, changes in peritubule capillary Starling forces have little effect on proximal sodium reabsorption. Thus, the physical factor mechanism is a rather insensitive regulator of proximal reabsorption in the absence of volume expansion. Hormones known to regulate sodium transport per se, such as aldosterone, have no effect on sodium reabsorption by the proximal tubule. In contrast, those hormones primarily regulating anion reabsorption in the proximal tubule, such as parathyroid hormone, have significant effects on fluid reabsorption. Thus, the humoral regulation of anion reabsorption has secondary effects on proximal sodium reabsorption.

Nonrecollection end-proximal tubule micropuncture technique and the microsphere method for estimating fractional distribution of renal cortical blood flow were applied to further define the mechanism of the natriuresis in the isolated dog kidney in response to volume expansion with equilibrated blood. Following volume expansion sodium excretion increased +79 plus or minus 24 muEq/min (P less than 0.01) in the face of significant decreases in inulin clearance (C IN) and renal blood flow (RBF) and in the absence of changes in renal perfusion pressure, plasma protein concentration or packed cell volume. (TF/P)IN of end-proximal tubular fluid decreased from 1.65 plus or minus 0.03 to 1.53 plus or minus 0.04, P less than 0.025, and proximal tubule absolute reabsorption decreased from 36 plus or minus 3 to 29 plus or minus 2 nl/min, P less than 0.05. The decrease in absolute reabsorption, however, was balanced by a decrease in single nephron GFR (SNGFR) so that no increase in distal delivery of fluid (V TF) out of the proximal tubule was detected. SNGFR/C-IN remained constant. No change in fractional distribution of RBF was detected. The data indicate that volume expansion with equilibrated blood depresses proximal tubule fractional and absolute reabsorptive rates in the isolated kidney but since V-TF did not increase, they imply that the natriuresis derives from a decrease in sodium transport along more distal nephron segments.

To explain how hydrostatic pressure differences between tubule lumen and interstitium modulate isotonic reabsorption rates, we developed a model of NaCl and water flow through paracellular pathways of the proximal tubule. Structural elements of the model are a tight junction membrane, an intercellular channel whose walls transport NaCl actively at a constant rate, and a basement membrane. Equations of change were derived for the channel, boundary conditions were formulated from irreversible thermodynamics, and a pressure-area relationship typical of thin-walled tubing was assumed. The boundary value problem was solved numerically. The principal conclusions are: 1) channel NaCl concentration must remain within a few mOsm of isotonic values for reabsorption rates to be modulated by transtubular pressure differences known to affect this system: 2) basement membrane and channel wall parameters determine reabsorbate tonicity; tight junction parameters affect the sensitivity of reabsorption to transmural pressure; 3) channel NaCl concentration varies inversely with transmural pressure difference; this concentration variation controls NaCl diffusion through the tight junction; 4) modulation of NaCl diffusion through the tight junction controls the rate of isotonic reabsorption; modulation of water flow can increase sensitivity to transmural pressure; 5) no pressure-induced change in permeability of the tight junction or basement membrane is needed for pressure to modulate reabsorption; and 6) system performance is indifferent to the distribution of active transport sites, to the numerical value of the compliance function, and to the relationship between lumen and cell pressures.

In Wistar rats with surface glomeruli 3 h of nearly complete occlusion of the left renal artery resulted in uniform falls (similar to50%) in ipsilateral whole-kidney glomerular filtration rate (GFR) and single-nephron GFR (SNGFR) and in urinary findings consistent with impaired water reabsorption. Since the fall in SNGFR was accompanied by a proportional fall in glomerular plasma flow rate (GPF), and since net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary was unchanged from preischemic levels, these findings suggest that the fall in SNGFR was a hemodynamic consequence of the fall in GPF. To test this hypothesis, GPF was restored to preischemic levels by means of acute infusion of homologous, isoncotic plasma. GPF and SNGFR uniformly increased, on average to preischemic levels, whereas net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary again remained essentially unchanged. These studies demonstrate that the fall in SNGFR in this model of ischemic injury is causally related to the accompanying fall in GPF. Of interest, despite this reversal of the defect in GFR, fractional water reabsorption remained impaired. This restoration of GFR but not reabsorption by plasma infusion abruptly converts this ischemic lesion from nondiuretic to diuretic.

To study the mechanism of phsophate reabsorption by the proximal tubule and the effect of parathyroid hormone (PTH), microperfusion experiments were carried out in rats. Segments of proximal tubule isolated by oil blocks were perfused in vivo with one of three solutions, each containing 152 meq/liter Na(+) and 2 mmol/liter phosphate, but otherwise differing in composition. The pH of solution 1 was 6.05-6.63, indicating that 60-85% of the phosphate was in the form of H(2)PO(4) (-). The pH of solution 2 was 7.56-7.85, and 85-92% of the phosphate was in the form of HPO(4) (=). Solution 3 contained HCO(3) (-) and glucose and had a pH of 7.50-7.65. When the proximal tubules were perfused with solution 1, the (32)P concentration in the collected perfusate was found to be consistently lower than in the initial perfusion solution. In sharp contrast, when the tubules were perfused with solutions 2 or 3, (32)P concentration usually rose above that in the initial solution. Water (and persumably Na(+)) reabsorption, as measured with [(3)H]inulin, was the same with the acid and alkaline solutions. Administration of partially purified PTH clearly prevented the fall in phosphate concentration with the acid solution, but had a less discernible effect on phosphate reabsorption with the two alkaline solutions. Measurements of pH within the perfused segments with antimony microelectrodes demonstrated that PTH enhanced alkalinization of the acid perfusion solution. The findings are consistent with the view that H(2)PO(4) (-) is reabsorbed preferentially over HPO(4) (=). This can be attributed to either an active transport mechanism for H(2)PO(4) (-) or selective membrane permeability to this anion. PTH appears to either inhibit an active transport process for H(2)PO(4) (-), or to interfere with passive diffusion of phosphate by alkalinizing the tubular lumen.

Our objective was to produce reductions in the luminal volume of Henle's loop and increases in linear flow velocity through the loop. We did this in a recollection micropuncture study by collecting fluid with and without suction from early distal tubules. With suction, transit time of fast green dye through the loop decreased by 34%, calculated loop volume decreased by 28%, and fractional water reabsorption fell from 73.6 to 70.3% (p smaller than 0.025) in water diuretic rats. Absolute water reabsorption did not decrease significantly. In urea-saline dieuretic rats transit time decreased 25%, calculated loop volume decreased 22%, fractional reabsorption fell from 59.0 to 51.7% (smaller than 0.001), and absolute reabsorption decreased by 2.3 nl/min (p smaller than 0.025). Single nephron glomerular filtration rate, distal tubular sodium concentration, and osmolality were unaffected. The less pronounced effect of collection with suction in water diuretic rats may be related to the lower medullary fluid osmolality, which was 338 plus or minus 9 (S.E.) mOsmol/kg as compared to 497 plus or minus 35 in urea saline diuretic rats. Collecting fluid with suction from late proximal tubules did not alter glomerular filtration rate or fractional water reabsorption. Stumpe et al. ((1970) J. Clin. Invest. 49, 1200-1212) noted an inverse correlation between fluid reabsorption from Henle's loop and flow velocity in rats with hypertension or congestive heart failure. One can reproduce this correlation by artificially altering the transmural pressure gradient in the loop.

126 micropunctures were performed on 40 Bowman's capsules as well as along the corresponding proximal convoluted tubules (PCT) on six nondiuretic rats. Capsular and tubular fluid samples (GF and TF) collected were analysed for Na, Cl, K, P, Ca Mg and 3H-Inulin concentrations by electron probe analysis and liquid scintillation. Electrolyte handling along the usually inaccessible part of the PCT, i.e. EPCT, was determined by selecting from the samples collected in the first two or three proximal loops, those having a (TF/GF) In value smaller than or equals to 1.15. Except for Na the concentration of electrolytes was significantly modified when the fluid flowed along the PCT: 1. In the EPCT, (TF/GF)Cl and K rose and (TF/GF)P dropped in correlation with (TF/GF)In. For (TF/GF)In = 1.15, (TF/GF) chloride, potassium and phosphate were respectively equal to 1.12, 1.10 and 0.72. These values were comparable to thoose obtained in the remaining length of PCT, indicating that the chemical gradient established in the first loops was maintained in the subsequent ones. Therefore proximal handling of these three ions differed depending on the PCT portion considered. The reasons for this difference are discussed further on. 2. Calcium concentration increased and reached a plateau corresponding to (TF/GF)Ca = 1.22 for (TF/GF)In values ranging from 1.31 to 1.45. 3. Magnesium was not reabsorbed for (TF/GF)In values below 1.90. Above this level slight Mg reabsorption occurred. 4. Significant correlations between (TF/GF)K, Ca and P and (TF/GF)Cl ratios were observed along the PCT, suggesting that proximal reabsorption of K, Ca and P was dependent on tubular fluid acidification.

In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both hormones produced elevations in single nephron filtration fraction due to declines in glomerular plasma flow with little change in nephron glomerular filtration rate. The resulting large increases in the efferent arteriolar oncotic pressure, piE, were accompanied by equivalent increases in the mean glomerular transcapillary hydraulic pressure difference, deltaP. Equality of piE and deltaP, denoting filtration pressure equilibrium, obtained before and during infusion of either hormone. Por both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases in AP were prevented by partial aortic constriction increases in resistance were confined primarily to the efferent arteriole. Tespite the marked increases in piE, absolute rates of proximal tubule fluid reabsorption, on the average, were unchanged by these hormones due to the opposing effects of marked decreases in efferent arteriolar plasma flow rate and, to a lesser extent, increases in peritubular capillary hydraulic pressure.

Active transport potentials were studied across early loops of rat proximal tubule during luminal perfusion and peritubular superfusion with HCO3- Ringer's solution of identical ionic composition. From the effects of the carbonic anhydrase inhibitor acetazolamide and of ouabain it is concluded 1. that the lumen-positive active transport potential indicates an excess of active H+ secretion/HCO3- absorption over active Na+ absorption and 2. that the lumen-negative active transport potential, which develops in the presence of glucose (and/or aminoacids) in the tubular lumen, indicates stimulation of active Na+ absorption. Ouabain did not abolish the lumen-positive potential difference suggesting that active H+/HCO3- transport and active Na+ transport may be to some extent independent. Among the diuretics tested the mercurial diuretic mersalyl acted primarily on Na+ transport, and furosemide acted on HCO3- transport, whereas the effect of ethacrynic acid appeared to be unspecific.

Models for coupling of salt and water transport are developed with two important assumptions appropriate for leaky epithelia. (a) The tight junction is permeable to both sale and water. (b) Active Na transport into the lateral speces is assumed to occur uniformly along the length of the channel. The proposed models deal specifically with the intraepithelial mechanism of proximal tubular resbsorption in the Necturus kidney although they have implications for epithelial transport in the gallbladder and small intestine as well. The first model (continuous version) is similar to the standing gradient model devised by Diamond and Bossert but used different boundary conditions. In contrast to Diamond and Bossert's model, the predicted concentration profiles are relatively flat with no sizable gradients along the interspace. The second model (compartment version) expands Curran's model of epithelial salt and water transport by including additional compartments and considering both electrical and chemical driving forces for individual Na and Cl ions as well as hydraulic and osmotic driving forces for water. In both models, ion and water fluxes are investigated as a function of the transport parameters. The behavior of the models is consistent with previously suggested mechanisms for the control of net transport, particularly during saline diuresis. Under all conditions the predicted ratio of net solute to solvent flux, or emergent concentration, deviates from exact isotonicity (except when the basement membrane has an appreciable salt reflection coefficient). However, the degree of hypertonicity may be small enough to be experimentally indistinguishable from isotonic transport.

Using radioimmunoassay techniques, arteria (A) and renal venous (RV) plasma renin activities were measured in sodium pentobarbital-anesthetized dogs during clearance and stop-flow periods. Changes in RV-A renin were used to estimate changes in renin secretion. RV-A renin increased during stop flow from its average value during clearance periods, whether 10% mannitol in 0.15 M NaCl or 10% mannitol in 0.1 M Na2SO4 was being administered intravenously. However, RV-A renin during mannitol + NaCl stop-flow periods was significantly greater than during mannitol + Na2SO4 stop-flow periods. Distal tubular fluid Na concentrations as indicated by stop-flow analysis were higher during the latter. These observations suggest that a macula densa stimulus, Na concentration, and/or load, may control renin secretion during ureteral occlusion.

The electrical potential difference (PD) in the rat proximal convoluted tubule was investigated in vivo as a function of distance from the glomerulus. The PD was found to be invariably negative (up to -4.5 mV) in the earliest segments (less than 0.5 mm from the glomerulus) and rose to positive values (+2 to +4) in the later segments (1 mm beyond the glomerulus). This change in PD correlated with the bubule fluid-to-plasma (TF/P) chloride ratios, which rose from unity in the early segments to approximately 1.3 in the late. Corresponding changes in PD and chloride ratios could be elicited by single-nephron stop-flow techniques in the early segments. Luminal perfusion techniques demonstrated a direct relationship between PD and tubule fluid chloride concentration. Acetazolamide was found to significantly reduce both late proximal PD (less than +2 mV) and TF/P chloride ratios (less than 1.06). Split-drop studies demonstrated that the negative PD in the early proximal tubule was dependent on the presence of glucose and alanine and the absence of a chloride gradient, whereas in the late proximal tubule under the same conditions the PD was not significantly different from zero. In this segment of the nephron the positive PD in free flow appeared to result from the chloride diffusion potential generated by preferential HCO3 reabsorption. These results provide further demonstration of intrinsic differences in the transport properties along the length of the proximal convoluted tubule.

This review focuses on the segmental handling of sodium during alterations in extracellular fluid volume. There is abundant evidence that proximal tubular sodium reabsorption is inhibited by Ringer loading but there are also unequivocal data demonstrating that inhibition of a more distal nephron segment is required for a maximal natriuretic response. From the evidence at hand presently, it would seem that, of the distal nephron segments, only the collecting duct is inhibited by expansion of the extracellular volume per se.

To determine if an increase in the endogenous secretion of parathyroid hormone could decrease sodium reabsorption by the proximal tubule, the ionized calcium concentration of blood perfusing the parathyroid gland of eight unilaterally thyroid parathyroidectomized dogs (TPTX) was reduced by infusion of an isotonic sodium citrate plus sodium chloride solution into the blood supply of the parathyroid gland. The fractional clearance of phosphate increased significantly (+9.3 +/- 2.8 ml/min per 100 ml GFR), while fractional sodium reabsorption by the proximal tubule decreased (-.06 +/- .02; P less than .025). In seven normal control dogs that received isotonic sodium chloride infusion, neither fractional sodium reabsorption by the proximal tubule nor the fractional clearance of phosphate was significantly altered. In five bilaterally TPTX dogs that received a sodium citrate plus sodium chloride infusion, sodium reabsorption by the proximal tubule was not significantly altered. There were no significant changes in glomerular filtration rate or renal plasma flow in any of these groups. The data demonstrate that alterations in endogenous parathyroid hormone secretion can play a significant role in the regulation of sodium reabsorption by the proximal tubule.

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and the mechanisms involved in these responses. Denervation was produced in anesthetized nondiuretic rats by application of phenol to the left renal artery. Studies were also performed in sham-denervated nondiuretic rats. Whole kidney and individual nephron studies were performed before and after denervation or sham denervation. Denervation increased urine volume from the left kidney to about twice its control value (P less than 0.001) and increased urinary sodium excretion from 332 neq min minus -1 to 1,887 neq min minus -1 (P less than 0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. The innervated right kidney showed no changes in urine volume or in sodium excretion. After denervation, late proximal ratio of tubular fluid inulin concentration to that of plasma [(F/P)In] decreased from 2.23 to 1.50 (P less than 0.001) while single nephron GFR remained unchanged. Absolute reabsorption decreased from 16.5 to 9.9 n. min minus -1 (P less than 0.001). (F/P)In ratios were also decreased in early distal (from 6.21 to 3.18, P less 0.001) and late distal convolutions (from 16.41 to 8.33, P less than 0.001) during the experimental period. (F/P)Na ratios remained unchanged in the early distal convolutions, but increased from 0.18 to 0.38 (P less than 0.01) in late distal convolutions after denervation. Absolute Na reabsorption after denervation increased in the loop of Henle, distal convolution, and collecting ducts. Any changes in intrarenal hydrostatic pressures after denervation were always small. There were no changes in GFR, RPF, urine volume, urinary sodium excretion, or late proximal (F/P)In after sham denervation. We conclude that the diuresis and natriuresis seen after acute renal denervation were caused by a marked depression of sodium and water reabsorption in the proximal tubule with partial compensation in more distal nephron segments. These responses appeared to be unrelated to systemic or intrarenal hemodynamic changes. The results demonstrate an effect of the renal nerves on proximal tubular function.

The results of our previous studies have suggested that serum-induced inhibition of proximal tubular fluid absorption is due to complement-induced lysis of the tubular cells. The present study provides further evidence in support of this idea as well as other information pertinent to the mechanism of complement activation in vivo. 1. The electrical resistance of the luminal brush border membrane is reduced drastically concomitantly with a drop in cell potential difference when serum is perfused intraluminally. 2. Human C1 inhibitor (30-50 units/ml) does not significantly affect the inhibitory activity of human serum on fluid absorption, suggesting the non-involvement of the classical pathway. 3. Reactive lysis reagents (C56, C7, C8 + C9) partially inhibit fluid absorption when infused into the lumen. 4. In contrast to our previous report (Sato, K. and Ullrich, K.J. (1974) Biochim. Biophys. Acta 354, 182-187), very fresh serum, 10-times diluted can inhibit fluid absorption if perfused for 10 min. 5. Both mouse and guinea pig serum, which are normally inactive, are activated to attack the tubular cells if 1/100 volume rat or rabbit serum is added to them No such activation occurs by mixing guinea pig serum and mouse serum. The available data suggest that the presence of the later complement components but not the heat-labile factor (Factor B) or C3PA or C1 in the added serum is a prerequisite for mouse and guinea pig sera to be activated to inhibit fluid absorption.