There has been a large body of reports on the experimental renal hypertension. Recently, Muirhead reported that the hypertension could be prevented by the autoexplantation of renal tissue in the bilrterally nephrectomized dogs. His observation suggests that antihypertensive substances may be produced by the medullary tissue of healthy Kidneys. The study was carried out in dogs to further investigate this concept, by utilizing different techniques. Mongrel dogs, weighing 12-22 kg, were used for this experiment . A bilateral nephrectomy was performed in 2 dogs. The ureters were both ligated in 6 dogs. In 2 dogs was bilateral uretro-venous anastomosis done. Parenteral administration of the homogenate of the total Kidney following bilateral nephrectomy, in 2 dogs, the administration of the cortical homogenate following bilateral nephrectomy in 1 dog, and the administration of the medullary homogenate following bilateral nephrectomy in 2 dogs were also perfor med. These dogs were expired in a typical uremic state approximately 7 days postoperatively. A mean arterial pressure was measured daily by a mercury manometer until demise. The dogs with a bilateral nephrectomy demonstrated progressive and profound rise in arterial pressure with a daily increment of 14.3 mmHg. Blood pressure in the group of dogs with a bilateral ureter ligation was also rised progressively but much more slowly with a daily increment of only 8.1 mmHg. No significant alteration in blood pressure was noted in the dogs with a bilateral uretrovenous anastomosis during the experiment. There was little rise in blood pressure following the administration of homogenates of the total Kidney as well as the uretro-venous anastomosis. The elevation of blood pressure was marked in dogs with the intraperitoneal administration of the cortical homogenate, whereas there was pertically no elevation in dogs with the administration of the medullary homogenate. The above findings agree with Muirhead's observation and support the thought that an alive renal tissue mass plays a vital role in the maintenance of normotensive state, probably by producing antihypertensive substances.

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At the present time steroid therapy has become the most important procedure for nephrotic syndrome. It is felt that, in the earlystages, large dosage and long-term treatment is the most effective. Efforts have been made to elucidate the mechanism, but a definite criterion for this administra tion has not been established as yet. At first the steroid therapy was studied on clinical data and then experimentally, on Aminonucleoside induced nephrosis mainly from the phase of protein metabolism. Especially the research carried out on the synthesis and catabolism of protein in the liver and kidney, as the metabolic organs, which changed with the course of albuminuria or therapy. Furthermore, in some cases, the electron microscopic studies of the kidney were made. (I) (1) As to the clinical data of the adrenocortical steroid therapy, a proper dose may exist, in the form of Prednisolone 40-30 mg per day in the early stages and, as the maintenance therapy, 20 mg per day for 3 sucessive days of each week, and by this therapy 60.9 per cent of the patients were favourably effected. It is desireble to continue the maintenance therapy for a considerable long term, and it was found that even two months was not adequate for remission in some cases. (2) Methylandrostendiol and its derivatives were somewhat effective in improving the abnormality of blood chemistry. Their administration with Prednisolone was found more effective. (II) (1) Experimental Aminonucleoside induced nephrosis in rats, which was extremely similar to humans, might occure uniformely and the induction of the disease was explained by the inhibition of the disease was explained by the inhibition of the disease was explained by the inhibition of the nucleic-acid metabolism. (2) In the Aminonucleoside induced nephrosis, the synthesis of protein was increased in the liver and the catabolism of proteins was increased, also in the kidney. (3) As to electron microscopic findings, a confluence of foot process glomeruli was observed but no marked change occurred in the basement membrane, endothelial cells or mesangium. (4) In some cases, a confluence of foot process was seen before the onset of albuminuria, then protein filtration through glomerulus probrbly occurred in an increased amount. It may be thought that albuminuria sets in when the protein filtration exceeds the maximum tubuler protein re-absorption. (III) (1) Using various steroids to experimental Aminonucleoside induced nephrosis, it was noted that a large quantity of Prednisolone ; i. e. 1.0 mg/day, caused the most improvement in clinical picture, but considering the phase of the synthesis and catabolism of protein, 0.5 mg/day dosage might be adequate. (2) The administration 'of ACTH was not so effective. (3) The administration of anabolic hormones, didn't improve albuminuria, but was found to improve the abnormality of blood chemistry by the anabolic action. (4) The administration of Spirolactone was not favourable to protein metabolism but favourable to water and electrolyte metabolism.

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In an attempt to observe ATPase activity in cell membrane of the renal proximal table of the rabbit with Masugi-nephritis, the chemical determination of ATPase activity in the microsome fraction of kidney cortex accompanied with the histochemical stainning for ATPase was peaformed. In the cases with mild lesions in glomeruli and tubules under the light microscopic finding, the electron microscopic investigation implied marked vesiculation in the apical cell zone and pinocytosis and ATPase activity in cell membrane increased. However, in the cases wich severe damage in glomeruli and tubules under the light microscopic finding, the electron microscopic investigation showed the destruction of the cell membrane, particulary brush border and ATPase activity in cell membrane decreased. The proximal tubule cell of the normal rabbit kidney reabsorbed peroxidase of which molecular weight was similar to albumin, whereas peroxidase was not reabsorbed at all by the cell of which membrane ATPase activity was lowered. In conclusion, ATPase in the cell membrane seems to be important to maintain the elasticity and normal structure of the living cell membrane and in considered to be indespensable for membrane movement including pinocytosis and for energy transfer of high phosphate bond energy which is needed for active transport.

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The author performed pathological studies on the kidneys of 34 autopfy cases of essential hyper tension and arteriosclerosis, with special reference to the changes of vascular trees. According to the organ severely affected, the cases were divided into 4 types: renal type (malignant and benign nephrosclerosis), cerebral type (cerebral hemorrhage and encephalomalacia), myocardial type (coro nary sclerosis with or without infarction), and sclerotic aorta type (atherosclerosis and aneurysm of the aorta). The results obtained were summarized as follows. 1) The percentage of hyalinized renal arterioles (number of arterioles whose lumina are narro wed or obliterated by hyalinization of the wall/total number of arterioles found in two sections ×100) was 36, 26, 7 and 8% in renrl, cerebral, myocardial and sclerotic aorta type, respectively. 2) Fatty degeneration of the intima of renal arterioles occurred in two patterns, namely in the forms of granular and diffuse deposits. Severe granular fat deposits were found in the cases with severe hypertension, marked hypertrophy of the heart and clinical course of acute or subacute pro gression. Diffuse fat deposits were often found together with slight granular fat deposition in slowly advancing cases. 3) Interlobular arteries were divided into three portions: distal (50-100μ in the external diameter), intermediate (100-150μ) and proximal portion (150μ or more). Tempo of progress of hyper tension was most clearly represented by the histologic features of intima of the intermediate portion of interlobular arteries. Loose, concentric, fibrillary thickening of the intima was found in a case of malignant hypertension and 4 cases of benign nephrosclerosis with downhill course. Dense fibrillary thickening mixed with slight elastosis of the intima was found in 4 casef of benign nephrosclerosis with subacute progression. Fibro-elastic thickening of the intima was found in the cases with slowly advancing course. 4) Relationships between renal vascular changes and blood pressure, heart weight and ratio of heart and kidney weights. a) Percentage of hyalinized renal arterioles: Generally speaking, when the percentage was above 50, the systolic blood pressure was over 200 mmHg. and the ratio of heart and kidney weights was above 2.2. In the cases with the percentage from 10 to 30, the ratio was from 1.3 to 1.7, and in the cases with the percentage less than 10, it was less than 1.3. The relationships described above, however, were not always applicable to the cases of advanced age and acute or subacute progression. The relationship between the percentage and the heart weight was nearly the same as described abhve, b) The grade of narrowing of the lumina of interlobular arteries (external diameter-internal diameter/external diameter ×100) : When the mean value of this grade in three portions of interlobular arteries was above 50, the systolic blood pressure was often above 200 mmHg. And when the mean was above 54, the ratio of heart and kidney weights was frequently more than 2.0. 5) Nine cases of diffuse glomerulonephritis were studied in comparison with essential hypertension and arteriosclerosis. Pathological differentiation in these diseases was discussed.

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The author studied pathohistolo, gically the brain, heart, kidney and aorta of 37 cases with essen tial hypertension and/or arteriosclerosis and 9 case of diffuse glomerulonephritis. The patients of the former group are as follows: cerebral hemorrhage 10, encephalomalacia 3, and myocardial infarction 2, coronary arteriosclerosis 3, heart failure 2, malignant nephrosclerosis 'l, benign nephrosclerosis 10, and arterioscler otic contracted kidney 3. The results obtained are summarized, as follows: The vascular trees of the kidney, brain, and heart were divided into three segments : arteriole, medium-sized and large arteries. In essential hypertension and arteriosclerosis, the histologic changes in the corresponding segments in these organs were essentially the same. The localization of the main change seems to be decided by the tempo of progression of the diseases and by the age of the patients. When the patient is young and the progression of the diseases was rapid, the change was predominant in the kidney. When the age is above 40 and the progression is relatively slow, the main change was found in the brain. Sclerosis of coronary arteries began to develop in younger patients and progressed slowly. It was only in older patients that coronary arteriosclerosis pathohistologically induced myocardial damage, unless the heart was rapidly enlarged. In diffuse glomerulonephritis, the vascular changes were localized in the arterioles and interlobular arteries of the kidney. The changes were milder than in nephrhsclerosis.

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Serum sodium and potassium levels, urinary sodium, potassium, and aldosterone excretions have been determined with or without additional oral load of 135 meq, per day of potassium chloride in normals and patients with essential and renal hypertension and primary aldosteronism on diet containing constant amounts of sodium and potassium. In most of the patients with primary aldosteronism and the other hypertensives, the urinary aldosterone excretion before potassium load was higher than in normals but no significant difference was found between the two groups. The subjects with relatively lower serum potassium levels tended to show higher urinary aldosterone excretions. It was inferred, therefore, that the hypokalemia occasionally accompanying hypertensive diseases is due to increased secretion of aldosterone. After the beginning of potassium loading the urinary aldosterone excretion rapidly increased in normals and patients with primary aldosteronism, but only gradually in the other severe hypertensives. This suggested that the adrenals of severe hypertensives have a relative autonomy on aldosterone secretion, and that, on the other hand, in the patients with primary aldosteronism the marked hypokalemia prevents the production of aldosterone and, therefore, urinary aldosterone is not always more copious in them than in the other hypertensives; for this reason the urinary aldosterone excretion rapidly increases after potassium loading.The elevation of serum potassium level was more remarkable and the rate of increase of urinary aldosterone excretion was lower during the potassium loading in the subjects showing marked reduction of blood pressure in consequence of the potassium chloride administration, than in those showing no reduction of blood pressure. This was explained as follows : the reduction of blood pressure due to potassium chloride administration prevents the increase of aldosterone secretion contrary to the stimulating action of potassium on aldosterone secretion, and a remarkable elevation of serum potassium level is induced. There was no correlation between the degree of increase of urinary sodium excretion due to potassium load and the degree of the reduction in blood pressure or the rate of increase of urinary aldosterone excretion. And thus, it was suggested that the reducing effect on blood pressure and the stimulating effect on aldosterone secretion of potassium load are not realized through the mediation of urinary loss of sodium, but directly by the action of potassium on them. The loss of sodium during potassium chloride administration was greater in all kinds of hypertensives described above than in normals.

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