Proximal and distal tubular activity in chronically catheterized fetal sheep compared with the adult

Renal function was studied in unanaesthetized fetal sheep aged 112-120 and 126-132 days and in adult nonpregnant ewes. The clearance of lithium was used to measure proximal and distal fractional sodium reabsorption. In five nonpregnant adult sheep, 80.6 +/- 1.7% (SE) of the filtered sodium load was reabsorbed proximally and 18.2 +/- 1.53% distally. This was different from all groups of fetal sheep (p less than 0.001). In younger fetuses, proximal fractional sodium reabsorption was less (51.3 +/- 2.3% (SE), p less than 0.05) and distal fractional sodium reabsorption greater (42.4 +/- 2.3% (SE), p less than 0.05) than older fetuses (126-132 days old) in which 61.4 +/- 2.4% (SE) was reabsorbed proximally and 33.6 +/- 2.5% (SE) distally. In another group of fetuses aged 125-137 days, in which proximal tubular sodium reabsorption was measured after distal tubular blockade, proximal fractional sodium reabsorption was 57.8 +/- 2.95% (SE) and distal fractional sodium reabsorption, 38.7 +/- 2.64% (SE). In adult sheep there was no relationship between distal tubular sodium reabsorption and glomerular filtration rate, i.e., proximal tubular function was responsible for glomerulotubular balance. However, in the fetuses, both proximal and distal tubular sodium reabsorption contributed to glomerulotubular balance. Thus in fetal life, the proximal tubule participates to a lesser extent in reabsorbing the filtered sodium load possibly because its function is suppressed by its relatively "volume-expanded" state or because it is functionally immature. Therefore, a greater proportion is reabsorbed distally and the distal nephron participates under physiological conditions in glomerulotubular balance.     

Effects of alpha-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs.

The alpha-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 mug kg-1 min-1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic throacic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265+/56 (SEM) to 370+/65 muequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distalsodium load did not change significantly. In normal dogs, tubular sodium reabsorption decreased significantly from 73.4+/2.8% to 63.1+/4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of alpha-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased alpha-adrenergic activity does not play a significant role in the sodium retention of these animals.     

Magnesium reabsorption in the juxtamedullary loop of Henle: effect of magnesium deprivation

To determine the contribution of the juxtamedullary loop of Henle to magnesium reabsorption during magnesium deficiency, we performed two-phase micropuncture studies of end-descending limbs in a group of magnesium-deficient rats (n = 7) and in a pair-fed control group (n = 8) given MgCl2 in their drinking water. In the magnesium-deficient rats, daily excretion of magnesium fell to very low values (1.2 +/- 0.2 vs. 52 +/- 12 microM.day-1.100 g body weight-1, p less than 0.05). Plasma magnesium concentration and fractional magnesium excretion during the control phase were nearly 52 and 27%, respectively, of the values observed in pair-fed controls. Fractional magnesium delivery to the end-descending limb did not differ significantly between the two groups. During the acute magnesium repletion phase, fractional magnesium excretion and fractional magnesium delivery to the end-descending limb increased by a similar value in the two groups of rats, despite a lower filtered load of magnesium in the magnesium-deficient group. Absolute magnesium reabsorption upstream to the end-descending limb was lower in the magnesium-deficient rats but was otherwise tightly coupled to the filtered load of magnesium (Y = 0.91 + 0.37 x, r = 0.82, p less than 0.05). Similar observations were made with regards to whole kidney magnesium reabsorption. Our results suggest that, in young magnesium-deficient rats, magnesium reabsorption is tightly coupled to the filtered load of magnesium both in segments upstream to the juxtamedullary end-descending limb and in the whole kidney, and that a reabsorptive defect for magnesium is not evident in this setting.     

The actions of cortisol on fetal renal function

Renal function was studied in 6 fetal sheep, aged 126-135 days, before and after 3 injection of 15 mg of cortisol given at intervals of 12 h. Cortisol caused a significant rise in both renal blood flow (P less than 0.05) and glomerular filtration rate (P less than 0.005), and in urine flow rate (P less than 0.02) but it did not consistently cause a natriuresis. The urinary pH was unchanged following cortisol treatment, but bicarbonate excretion increased. Urinary phosphate excretion was increased (P less than 0.005) because of a rise in filtered phosphate and a fall in phosphate reabsorption. The titratable acid excretion increased (P less than 0.005) but urinary ammonium excretion did not. The total amount of sodium reabsorbed increased after cortisol but the amount of sodium reabsorbed in the proximal tubule did not increase, so fractional reabsorption in the proximal tubule decreased from 61.7 +/- 4.1% to 47.3 +/- 4.2% (P = 0.01). The total amount of sodium reabsorbed in the distal tubule increased and distal fractional reabsorption increased from 33.3 +/- 2.4% to 47.3 +/- 4.2% (P less than 0.01). Cortisol may increase the capacity of the immature kidney to play a role in fluid and electrolyte homeostasis by increasing glomerular filtration rate and delivering more sodium and water to the distal nephron where the reabsorption of sodium and water can be modified independently and in accordance with need.     

刺激脑内渗透压感受器对大鼠肾小管重吸收钠,氯,钾的影响

实验在麻醉大鼠上进行。用肾小管微穿刺技术观察到,脑室内注射高张盐水(icv.HS)后:(1)近曲小管末段钠残留分数从53.0±2.1％升高至66.0±2.9％(P<0.01);氯残留分数从65.4±3.4％升高至78.2±3.9％(P<0.05);钾残留分数和小管液渗透克分子浓度无显著变化。(2)远曲小管起始段钠残留分数从8.2±0.9％升高至13.6±1.8％(P<0.05);氯残留分数从5.4±0.8％升高至9.5±1.4％(P<0.05);小管液渗透克分子浓度从139.8±6.9mOsm/kg H_2O升高至181.3±15.6mOsm/kgH_2O(P<0.05);钾残留分数无显著变化。静脉注射速尿能消除icv.HS引起的尿钾增多反应,但不能消除icv.HS引起的利尿和尿钠增多反应。上述结果表明,刺激脑内渗透压感受器能抑制近曲小管中钠和氯的重吸收,并促进远曲小管及其以后部位的钠钾交换,导致尿钠排出增多和尿钾排出增多。     

Studies on Compensatory Adaptation of Renal Functions

Changes in the excretion of water and electrolyte in one kidney after exclusion of its partner have been studied in anesthetized dogs and rabbits. Complete clamping of the contralateral kidney pedicle or ureter results in a rapid increase in the excretion of water, sodium, potassium, chloride, calcium, phosphate and bicarbonate. This response is also observed in denervated kidneys. Pretreatment with the loop inhibitor, furosemide, does not preclude adaptation which, however, is blunted by acetazolamide, an inhibitor of proximal sodium and bicarbonate reabsorption. Free-water reabsorption during hypertonic saline diuresis is normal in the remaining kidney. Compensatory adaptation, thus, appears to be located in the proximal tubule. The regulatory response to contralateral kidney exclusion is already fully developed in one-month-old rabbits. Compensatory adaptation of electrolyte excretion is not accounted for by changes in extracellular fluid volume, plasma composition, glomerular filtration rate, effective renal plasma flow, aldosterone or vasopressin.     

Acute Functional Adaptation to Nephron Loss: Micropuncture Studies

The renal and proximal tubule response to contralateral kidney exclusion was studied in a variety of circumstances. Recollection micropuncture studies were performed to assess the response to contralateral kidney clamping in the normal or a remnant kidney of the dog. Acute clamping of the contralateral kidney for a normal and unilateral remnant kidney resulted in marked reduction in proximal TF/P inulin ratios in the experimental kidney reflecting a 15 percent reduction in fluid reabsorption. Mean fractional excretion of sodium, potassium and water increased significantly in remnant kidney dogs but no significant change was observed in normal dogs except for potassium excretion. The marked reduction in proximal reabsorption occurred as soon as 5-15 minutes after contralateral kidney clamping and was compensated by distal reabsorption. Acute obstruction of the contralateral ureter results in a similar markedly reduced proximal tubular reabsorption. The reduction in proximal reabsorption induced by contralateral clamping occurred in the presence of reduced perfusion pressure and volume expansion and to some extent with renal denervation. When prostaglandin E₂ or acetycholine were infused prior to contralateral kidney clamping, proximal reabsorption remained at control levels and the contralateral clamping response was blocked. Similar blockade occurred after treatment with indomethacin. Acute reduction in nephron mass causes a marked depression of proximal tubular sodium and fluid absorption not obviously accounted for by hemodynamicphysical factors and humoral factors may be involved. The level of distal reabsorption to increased proximal delivery following contralateral clamping, determines the net urinary excretion.     

Acute effect of salmon calcitonin on renal magnesium transport in the magnesium-loaded rat

The present studies were undertaken to examine whether salmon calcitonin, by increasing magnesium reabsorption in the thick ascending limb, and presumably the tubulointerstitial magnesium concentration gradient, would lead to an increase in fractional magnesium delivery to the end-descending limb (magnesium secretion) in magnesium-loaded rats. Thyroparathyroidectomized, postprandial Munich--Wistar rats were prepared for micropuncture of papillary end-descending limbs and of superficial end-accessible proximal tubules. Group 1 served as clonidine-water diuresis time controls; group 2 was treated as group 1 but also received synthetic salmon calcitonin (10 mU/min); and group 3 was treated as group 2 but also received calcium chloride intravenously. Calcitonin, alone or with calcium, produced a significant fall in fractional magnesium excretion. A significant relationship was also observed between fractional magnesium excretion and urine flow rate (r = 0.56, p less than 0.01). Calcitonin did not modify fractional magnesium delivery to the end-descending limb. A highly significant relationship was observed between tubule fluid-to-ultrafiltrate magnesium ratio and tubule fluid-to-plasma inulin ratio (r = 0.88, p less than 0.001). Within each group, fractional magnesium delivery to the end-descending limb was similar to the corresponding value in the superficial end-accessible proximal tubule. Our results suggest that despite intense magnesium reabsorption, presumably in the thick ascending limb, magnesium secretion does not occur in the juxtamedullary pars recta and (or) thin descending limb.     

Long-Term Responses to Loss of Renal Mass: Tubular Changes: Chronic Reduction in Renal Mass: Micropuncture Studies of Response to Volume Expansion and Furosemide

Chronic nephron loss is compensated by functional adaptations which preserve electrolyte homeostasis. The response to volume expansion and diuretics was tested in dogs. Three phase recollection micropuncture studies were performed to assess the response of the remnant kidney in various stages of renal failure to furosemide administration (10 mg/Kg) and graded volume expansion (3 percent and 10 percent body weight). After the diuretic maneuvers, mean fractional excretion of sodium, potassium and water rose progressively in normal dogs (Stage I), with a greater increase in the remnant kidneys in the presence (Stage II) and absence (Stage III) of the contralateral kidney. Proximal and distal TF/P _Inulin ratios were depressed after 3 percent volume expansion. However, proximal TF/P _Inulin was not further lowered after 10 percent volume expansion and furosemide administration, while distal TF/P _Inulin ratios were progressively depressed. The distal TF/P _Inulin ratios in Stage III were significantly lower than in Stage II under analogous conditions. Our results suggest that the adaptive increase in the response of sodium transport by the remnant kidney to the diuretic maneuvers occurs in the loop of Henle, both in the azotemic and the non-azotemic stage. Adaptation of potassium excretion, as revealed by distal micropuncture, took place in the azotemic Stage III. Chronic functional adaptation for electrolyte transport occurs even before azotemia in the distal nephron and includes the proximal tubule with azotemia.     

脑室内注射高张盐水抑制近曲小管对水和钠的重吸收

实验在麻醉大鼠上进行。用锂清除率为指标观察脑室内注射高张盐水对近曲小管重吸收水和钠的影响。在切断单侧肾神经的动物中,脑室内注射高张盐水后的锂清除率与肾小球滤过率比值在去神经侧肾脏从0.37±0.04增加至0.51±0.05(P<0.01);神经完好侧肾脏则从0.26±0.03增加至0.31±0.04(P<0.05);双侧肾脏的肾小球滤过率、尿量、尿钠和尿钾量均增加,且去肾神经肾脏的增加幅度高于肾神经完好肾脏。在肾小管微穿刺实验中,脑室内注射高张盐水后,近曲小管末段小管液流量从24.42±1.84nl/min增加至31.86±3.09nl/min(P<0.01),小管液的渗透压无显著变化。以上实验结果表明,脑室内注射高张盐水引起的利尿、尿钠增多反应与肾小球滤过率增加和近曲小管对水、钠重吸收减少有关,体液因素在该反应中可能起主要作用。     

Micropuncture study of the renal responses of the urodele amphibian Necturus maculosus to injections of arginine vasotocin and an anti-aldosterone compound.

1. Necturus maculosus kidney function has been examined using standard clearance techniques and renal tubular micropuncture methodology. 2. Throughout, cyanocobalamin (vitamin B12) has been used to monitor glomerular filtration rate (GFR) and tubular water movements. It was established that this substance was handled by the Necturus kidney in a similar manner to inulin. It can be readily analysed, together with renal electrolytes, by electron microprobe techniques. 3. Profiles of transtubular gradients (TF:P ratios) along the nephron were established for osmolarity, sodium, potassium, calcium and cobalt (of cyanocobalamin). 4. Ureteral urine is always hyposmotic with respect to plasma and the site of dilution of the plasma ultrafiltrate is within the distal segment. 5. Up to 30% of the filtrate is isosmotically reabsorbed along the proximal tubule; the tubular fluid:plasma ratio for osmolarity and sodium is around 1, and the TF:P for cobalt of cyanocobalamin is about 1.4 by the end of this segment. 6. The renal effects of the neurohypophysial hormone arginine vasotocin (AVT) and an aldosterone antagonist (SC14266; Soldactone) have been examined. 7. AVT was consistently antidiuretic causing both a decreased GFR and an enhanced distal tubular reabsorption of water. 8. SC14266 also increased distal tubular reabsorption of water. Such an effect differs from that found in higher vertebrates, and may indicate a "glucocorticoid-type" of renal action for aldosterone in amphibians.     

Alterations induced by large doses of furosemide in chronic renal insufficiency.

Eleven patients with different degrees of renal failure with creatinine clearances between 7 and 32 ml/min have been studied. After a standard water overload and control periods of clearances, furosemide 1 g was given/i.v. There followed significant increase of renal plasma flow and glomerular filtration rate. In one case the increase was maintained during a follow up period of 3 hours. A significant increase was evident in phosphate, uric acid, sodium, potassium, and calcium clearances, as well as an increase in the sodium delivery to the distal nephron and a decrease in tubular reabsorption of phosphate. All this may be interpreted as the result of renal vasodilation induced by furosemide and its effect upon the proximal tubule and on Henle's loop.     

Distal blockade in experimental glomerulonephritis: the role of the diluting segment in sodium retention

In the light of accumulating evidence implicating the diluting segment as the site of final regulation of sodium excretion by the nephron, we produced in this experiment distal blockade in anti-glomerular basement membrane (GBM) glomerulonephritic (GN) rats by the administration of furosemide and polythiazide. This allowed to dissociate the sodium reabsorption that occurs in the proximal tubule from the one that occurs more distally and permitted an appreciation of the r?le played by the diluting segment in the sodium retention of anti GBM GN. In a previous experiment we showed that GN conscious or anaesthetized rats presented an increase in Na tubular reabsorption and failed to raise their fractional and absolute excretion of sodium as normal one did after rapid volume expansion. In this study distal blockade corrected almost completely the difference in sodium excretion that existed between GN and normal groups before the administration of diuretics, pointing to the important r?le played by the diluting segment in the sodium retention of experimental GN.     

Long-Term Responses to Loss of Renal Mass: Tubular Changes: A Micropuncture Study of HCO3 Reabsorption by the Hypertrophied Proximal Tubule

In rats with renal failure produced by excision of one kidney and infarction of large portions of the other kidney, given a low calcium, high phosphorus diet for 2-3 weeks, GFR was reduced by 80 percent, the fractional excretion of sodium increased from 7 to 23 percent, that of bicarbonate from 16 to 23 percent and that of water from 4 to 13 percent. Single nephron GFR in the remaining nephrons was nearly doubled and end-proximal TF/P_In was depressed from 2.3 to 1.8, and proximal TF/P_HCO3 from 0.52 to 0.35, the latter figure corresponding to an increase of absolute proximal HCO₃ reabsorption from 1.7 to 3.5 nEq/min or from 2.8 to 3.2 Eq/L of single nephron glomerular filtrate. Acute parathyroidectomy had no influence on the fall of GFR or the rise of SNGFR in the remaining nephrons and failed to cause any significant changes in proximal tubular bicarbonate reabsorption. Parathyroidectomy, on the other hand, practically prevented the rise of the fractional excretion of sodium and of water and inverted the rise of the fractional excretion of bicarbonate to a fall. The data are interpreted to indicate that secondary hyperparathyroidism in renal failure impairs distal nephron bicarbonate and sodium reabsorption and, thus, contributes to the maintenance of sodium balance, but could possibly aggravate acidosis.     

Effects of increased perfusion pressure on medullary collecting duct function

The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 +/- 4.1 to 51 +/- 9.3% (p less than 0.01) and from 65.7 +/- 6.0 to 42.7 +/- 9.1% (p less than 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.     

Physiological analysis of various types of osmotic diuresis

Efficacy of drugs reduced proximal reabsorption was compared in experiments with female Wistar rats. Urine flow rate for the 1st h of experiment was enhanced after polyethylene glycol-400 (PEG) and 6% Na2SO4 infusion by over 30-fold, exenatide--40-fold, glycerol--11-fold as compared with the control. The maximal values of Na+ excretion were observed during Na2SO4 and exenatide administration (280 +/- 31 micromol/h vs. 3.2 +/- 0.6 Imol/h/100 g bw). The highest K+ excretion was revealed in experiments with glycerol administration (41 +/- 5 micromol/h vs. 7 +/- 2 micromol/h/100 g bw), Mg2+ --after exenatide injection (5.3 +/- 1.3 micromol/h vs. 0.16 +/- 0.03 micromol/ h/100 g bw). Diuretic effects were additive after combined administration of maximal doses of exenatide and PEG which suggests a different mechanism of action of solutes filtrated (PEG) to the proximal nephron segment and generated due to Na+/HW-exchange inhibition (exenatide). Osmotic diuretics differ by potency, mechanism of diuretic action and selectivity of ion excretion).     

Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep

These experiments examined whether renal growth and the fetal renin-angiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 +/- 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses (P < 0.05), and renal angiotensinogen mRNA levels were approximately 2.6-fold higher (P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed (P < 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were approximately two-fold higher throughout infusion (P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 +/- 6.5 to 53.7 +/- 10.2%), did not return to control levels (36.1 +/- 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 +/- 25 to 261 +/- 75 mumol/min by day 7, P < 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, long-term amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.     

The effect of renal arterial infusion of albumin and dextran on tubular fluid reabsorption in the dog.

Albumin or Dextran solutions of varying concentration were infused into the renal artery of hydropenic dogs. Their effect on urine flow, sodium excretion, creatinine and PAH clearance, single nephron GFR, fractional and absolute fluid reabsorption in the proximal convolution, reabsorptive t1/2, and hydrostatic pressures in the proximal tubules and adjacent capillaries was compared with a similar infusion of isotonic saline solution. Six, 9, 12, 18 and 25% albumin and 6% Dextran solution did not significantly change the measured parameters. Infusion of 9 and 12% Dextran solution elicited a decrease in water and sodium excretion as well as absolute and fractional proximal tubular fluid reabsorption to a 5% level of significance. Infusion of 18% Dextran was accompanied by a marked decrease in total and proximal reabsorption combined with a decline of GFR, PAH clearance, and hydrostatic pressures in tubules and peritubular capillaries. The results do not support the hypothesis of a direct action of oncotic pressure on tubular fluid reabsorption; the above described effects of Dextran seem to be accounted for by its other "pharmacological" effect.     

Role of V1- and V2-receptors in mechanism of physiological paradox--an increase of reabsorption of the solute free water and simultaneous rise of diuresis

In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.     

Effect of single dose of diuretics on renal magnesium excretion in man, with special reference to their site of action.

The administration of a single dose of furosemide, ethacrynic acid and polythiazide to healthy individuals under conditions of maximum water diuresis produces a significant increase in renal magnesium excretion. Elevated Mg excretion displayed a direct correlation to renal sodium excretion after furosemide (r=0.689, p less than 0.001), ethacrynic acid (r=0.869, p less than 0.001) and polythiazide (r=0.586, p less than 0.01). The slopes of the various regression lines did not differe significantly from each other or from the slope of the regression line characterizing this correlation for mannitol (r= 0.603, p less than 0.01). A significant linear correlation was likewise found between the excretion of Mg and total osmotically active substances after furosemide (r=0.783, p less than 0.001), ethacrynic acid (r=0.88, p less than 0.001) and polythiazide (r=0.646, p less than 0.01). The regression lines of the given correlations did not differ significantlyfrom each other, but their slopes were significantly higher than that of the regression line for the correlation after mannitol (r=0.454, p less than 0.01). The findings indicate that tubular Mg transport is influenced both by a decrease in tubular Na resorption in the diluting segment (polythiazide) and by an effect on Na resorption in the parts of the nephron proximal to the diluting segment of the nephron (furosemide, ethacrynic acid).