It is generally accepted that cortisol enhances sodium transport at the ascending limb. However, mechanism of the action has not been clearly defined. There are two possible explanations for the mode of action at the site. Cortisol may stimulate directly a pumping out sodium from the cell at the ascending limb into the peritubular fluid. The second possibility is an enhancement of sodium supply from the more proximal sites to the ascending limb, resulting in an increase of inward diffusion of sodium across the luminal membrane of the cell. Therefore, the study was undertaken on purpose to define which is the case. Two experiments were performed on 7 healthy students (age 19-21). In one experiment the subjects were fed normal sodium diets and in the other were fed low sodium diets (salt 3-4 g/day). Both diets contained 80 g of protein and were otherwise normal in composition, which were given for 2 days before experiments. All studies were performed under maximally hydropenic states after a 14-hour fast and 11 hours after the intramuscular injection of 5 U. of vasopressin tannate in oil. At 8: 30 a. m. on the day of the experiment 100 mg of cortisol was injected. Placebo experiments were performed after or before an interval of a week. Urine was collected at 60-minute intervals. All urine specimens were analyzed for sodium, potassium, chloride, urea and osmolality. Urine nonurea-solute (NUS) concentration was calculated as an index of medullary one. Cortisol injection decreased sodium excretion and the decrement was almost the same in the normal diet experiments as in the salt-depleted one. This was not attributed to an enhanced reabsorption of sodium at the distal nephrone, the mechanism of which is sodium/potassium exchange, because there was no change in potassium excretion in the experiments. It is reported that sodium transport at the ascending limb is indicated by an alteration in urine NUS concentrations, because NUS concentration in the medulla and collecting duct fluid have been shown to be the same in any plane cut perpendicular to the axis of the medulla under hydropenic conditions. Cortisol injection increased urine NUS concentrations. An increment in the salt-depleted subjects, however, was significantly less than noted in the subjects on nermal diets. This indicates that an increase in sodium transport at the ascending limb in the salt-depleted subjects is much smaller than that noted in the normal diet group. Therefore, the decrement in sodium excretion due to cortisol in salt-depleted subjects could not be explained by an increase of sodium reabsorption at the ascending limb. In addition, cortisol injection produced no significant alteration in creatinine clearance. This suggests that there was no decrement in the filtered sodium. It is apparent, therefore, that in the salt-depleted subjects cortisol injection resulted in an enhancement of sodium rebsorption at the proximal tubule, which caused sodium excretion to decrease. As above mentioned, if the mode of action of cortisol at the ascending limb is indirect one, sodium supply to the site should increase. On the contrary, it has decreased becouse of accelerated reabsorption at the proximal. tubule. It is concluded that cortisol stimulates directly an active transport of sodium at the ascending limb.

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It is generally accepted that cortisol enhances sodium transport at the ascending limb and augments the sodium/potassium exchange mechanism in the late distal tubule and collecting duct. However, the influence of cortisol on the sodium transport at the proximal tubule has not been thoroughly investigated. In the studies to be reported here, we have attenpted to pursuit the mode of action of cortisol at the proximal tubule with the assumptions that enhancement of sodium transport at the ascending limb due to cortisol could be suppressed by ethacrynic acid and sodium/potassium exchange mechanism at the late distal tubule by triamterene. Six healthy students (age 29-21) Were supplemented with large amount of salt (30 g/day) for 2 days in advance. All studies were performed under maximally hydropenic states after a 14-hour fast and 11 hours after the intramuscular injection of 5 U. of vasopressin tannate in oil. Two studies were performed on all subjects. In one experiment cortisol was administrered and in the other a placebo injection was given. At 8:00 a. m. on the day of the experiment 100 mg of cortisol was injected intravenously and 25 mg of ethacrynic acid and 50 mg of triamterene were given perorally 30 minutes later. Urine was collected at 60-minute intervals before and after administration of cortisol. All urine specimens were analyzed for sodium, potassium, chloride, urea and osmolality. Osmolalities were determined with a Fisk osmometer. In addition, nonurea-solute concentration was calculated as an index of medullary nonureasolute concentration. Because of administration of ethacrynic acid and triamterene, urine volume markedly increased, which, however, was not influecced by cortisol. On the contrary, the increment in sodium excretion was significantly less after cortisol than that noted in the placebo studies (p<0.02). Potassium excretion rose slightly but significantly after cortisol administration (p<0.01). Since the small increment was not enough to explain the total amount of decrease in sodium excretion, it seemed apparent that the enhancement of sodium/potassium exchange mechanism after cortisol was sufficiently inhibited, although not completely. Ethacrynic acid administration resulted in the marked decrease in non-urea solute concentration even in the cortisol studies, suggesting that active transport of sodium at the ascending limb was almost completely abolished. In addition, the mean change of glomerullar filtration rate was not statistically significant and was within the expected experimental error. Therefore, this study indicates that augmented proximal reabsorption contributes mostly to the decrement in sodium excretion after cortisol administration in the present experimental conditions.

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The administrations of glucocorticoid in normal rabbits for 6 weeks produced exudative lesions in the renal glomeruli. In the animals, in which the injection of heparin was started after, just at the time of, or even before the glucocorticoid treatment, a higher frequency of the occurence of those lesions was observed. In the animals, which were given warfarin simultaneously with corticosteroid, the occurence of those lesions were markedly inhibited. In the rabbits treated with heparin or warfarin alone, no such lesions were found. The concentration of NEFA in plasma rose up to abnormal high level. It was markedly higher in the animals treated with both glucocorticoid and heparin than in those treated with glucocorticoid alone. No increase of NEFA was noted in the rabbits treated with both glucocorticoid and warfarin. It is assumed from these results that the steroid nephropathy in the rabbit may be caused by an in-creased mobilization of NEFA, followed by the acceleration of blood coagulation process as secondary phenomen. The renal lesions seen 4 weeks after the injection of glucocorticoid has gradually regressed, if the injection was discontinued at that time.

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In order to investigate effect of metabolites in chronic renal failure on enzymes of TCA cycle and some others, enzyme activities in cortex homogenate of rabbit kidney, that were mixed with ultrafiltrate from the serum of uremic individual, were measured. Furthermore, effect of urea, potassium and ammonia on the enzyme activity were investigated in vitro. The results were as follows, 1) ICDH activity decreased on the 7 th day after homogenate was mixed with the ultrafiltrate from uremic individuals, on whom repeated hemodialysis was not perfmed, but LDH, MDH, l-GLDH and G-6-PDH activities did not change. 2) ICDH, LDH, MDH, l-GLDH and G-6-PDH activities did not change by the ultrafiltrate from uremic patients performed hemodialysis. 3) Both urea and potassium did not show any effect on ICDH activity, though their used concentration were higher than the value, we generally experience in renal failure. 4) As soon as ammonia in about 2 holds concetration of the normal blood was added to the homogenate, ICDH activity decreased to 53%, and was inhibited completely on the 7 th day. 5) G-6-PDH activity decreased to 88% by the effect of ammonia on the 7 th day, but the other enzyme activities did not change. 6) It is thought that the cause of inhibition of ICDH activity has relationship with both the enzyme protein and the Coenzyme. From these experimental results, it seems that the energy production by carbohydrate metabolism is disturbed by abnormal serum metabolites as well as renal ischemia and decrease of nephron-population in renal failure.

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This is the reports of the study on Enzyme activity in urine. U-LDH activity and U-LDH isozyme were studied in various subjects especially in hypertensive patients with and without renal involvements, and correlation of U-LDH and clinical findings was investigated. The results were summarized as follows. 1. Elevation of U-LDH activity and change of U-LDH isozyme pattern were observed in hypertensive patients associated with renal disorders or parenchymal renal diseases. Furthermore, urine obtained from patients with renal insufficiency showed an increased content of LDH₃, LDH₄ and LDH₅, with the predominant increase in LDH₃. The prognosis of the patients, Whoes U-LDH₃ was greater than 20%, was grave. These elevation and change, however, gave no indication of the etiology. 2. No correlation was obtained between serum and urine, in LDH activity and LDH isozyme. 3. U-LDH activity was directly proportional to urinary protein content, but has no correlation with other clinical and laboratory findings i. e. BUN, PSP, GFR, RBF. 4. Percentage of U-LDH₃ was directly proportional to BUN and inversely proportional to PSP or GFR, but there was a low statistical correlation between U-LDH₃ and urinary protein. 5. LDH isozyme patterns showed similarity between urine and renal tissue extracts in patients with renal insufficiency. 6. Determination of U-LDH activity and U-LDH isozyme is valuable as s supplement to the diagnosis of renal disorders in hypertensive patients.

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Following hypophysectomy changes in proximal convoluted tubules observed in the rat kidney. Wistar male rats with body weights of 80 to 100 gm. had, the pituitary removed by the transauditory method of Koyama. The rats were housed in individual cages, the urine was collected, and the daily volume was recorded. Several operated rats were sacrificed at 10 and 14 days after the operation. Before hypophysectomy, rats had an average daily urine volume of 8.2 ml. After hypophysectomy, most rats exhibited considerable increase in urine volume. (average 12.5 ml.) Hypophysectomized rats showed, with electron microscopy, marked changes in the proximal convoluted tubules. After 10 days, many, large, irregular shaped inclusion bodies were prominent in hypophysectomized rats. The inclusion dodies mainly located in the subnuclear position of the proximal convoluted tubular cells; whorls occured in the cytoplasm. Some cells showed the separation of the basal infoldings. After 14 days. many inclusion bodies with a single limiting membrane were located near the cell apex and they had dense or fine granular matrix. No other obvious changes were noted. We considered that the inclusion bodies were cytolysosomes. But in order to determine the exact nature of this bodies, we must prove the hydrolytic enzymes in the bodies.

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