Effects of angiotensin I-converting enzyme inhibitor (1-d-3-mercapto-2-methyl-l-oxopropyl-l-prolin, SQ 14225) on blood pressure, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were evaluated in 12 patients with essential hypertension, 4 with renovascular hypertension and 4 with chronic renal failure. The blood pressure began to fall within 15 minutes in both systolic and diastolic and reached a nadir between 60 and 90 minutes. Patients in the subgroup with pretreatment PRA greater than 2.0ng/ ml/h had a more decline in blood pressure ; after 60 minutes treatment, the depressor response in this group was also greater in magnitude than in the subgroup with pretreatment PRA less than 2.0 ng/ml/ h (26.1±10.7% versus 15.5±5.6%, P<0.05, in systolic blood pressure ; 25.0±17.8% versus 15.5±7.5%, P<0.02, in diastolic blood pressure. respectively). In this entire group of patients, there was a highly significant relationship (r=-0.822, P<0.001, in systolic blood pressure ; r=-0.714, P<0.001, in diasto-lic blood pressure, respectively) between the pretreatment PRA and the fall in blood pressure occuring at 60 minutes after administration. However, of 12 patients with essential hypertension, 3 patients whose PRA were below p. 5ng/ml/h showed a considerable fall in blood pressure. PRA increased from 2.09±2.74 ng/ml/h to 6.67±7.84 ng/ml/h in essential hypertension, from 4.78 ±1.62 ng/ml/h to 12.40±5.69 ng/ml/h in renovascular hypertension, and from 6.15±5.35 ng/ml/h to 11.98±13.38 ng/ml/h in chronic renal failure, respectively, after 60 minutes treatment. On the contrary, PAC decreased from 10.23±6.35 ng/dl to 6.36±6. 10 ng/dl (P<0.05) in essential hypertension, from 18.95±3.26 ng/dl to 10.70±3.31 ng/dl (P<0.02) in renovascular hypertension, and from 20.58±8.96 ng/dl to 12.83±1.71 ng/dl (P<0.05) in chronic renal failure, respectively after 60 minutes treatment. However, there was no relationship between change of PAC and change of blood pressure, while PAC increased inversely correlated with pretreatment PRA (r=-0.811, P<0.001). From these findings descrebed above, it is concluded that rapid antihypertensive effect of this inh-bitor is caused by supression of endogenously forming of angiotensin II.

View full abstract

The antihypertensive effect of orally active angiotensin converting enzyme inhibitor SQ14, 225 (Captopril) was assessed along with its influence on renin-angiotensin-aldosterone system and on renal function in nine patients with malignant hypertension. Of these, three had essential hypertension, two had renovascular hypertension, three had hypertension in association with chronic glomerulonephritis, and one patient did have a hypertension as a part of the systemic lupus erythematodes (SLE). Three of the nine patients were receiving no antihypertensive drug before this study was undertaken, whereas the remainder had already been treated with various combinations of diuretics and sympatholy-tic agents prior to this study. Arterial pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma cortisol concentration (PCC), effective renal plasma flow (RPF), glomeruiar filtration rate (GFR), and filtration fraction (FF) were determined during oral administration of SQ14, 225. Mean arterial blood pressure fell from 165±4 to 121±6 mmHg in eight patients. It is noteworthy that these patients responded well to the firse single dose of SQ14, 225. The depressor effect, however, was not observed in a patients with SLE who had had received previous treatment consisting of furose. mile and prednisolone. Orthostatic hypotension occured with the first single dose of 25mg in a patient who had previously received antihypertensive therapy with labetalol 600mg/day, furosemide 160mg/day and hydralazine 150mg/day. PRA markedly increased from 5.8±1.1 (mean SE) to 12.7±1. 7ng/ml per hr. These increase in PRA were thought to be mainly a reduction of a negative feedback mechanism of angiotensin II on the juxtaglomerular apparatus. Moreover, it is assumed that the reduction of blood pressure by SQ 14, 225, if not always present, might have also contributed to elevation of PRA through a compensatory reflex increase to svmnathetic traffic to the kidney. PAC decreased from 20.9±2. 1 to 9.4±1.9 ng/dl, while PCC failed to change significantly. These decreases in PAC are considered to be related to the reduction of angiotensin II caused by SQ 14, 225. RPF increased from 98±35 to 140±52 ml/min. However, there was no significant change in GFR. FF decreased from 0.36±0.03 to 0.25±0.04. These findings suggest that SQ14, 225 diminishes constriction of the efferent arterioles of the glomeruli. Skin rash or an impairment of taste sense was observed in a different single case during the treat-ment with 300mg/day of SQ 14, 225. It is concluded that the present study has not fully defined the exact mechansim by which SQ14, 225 loweer.s the blood pressure. Nevertheless, SQ14, 225 may well be employed as one of the first line choices in the treatment of patients with malignant hypertension.

View full abstract

Renal biopsy was performed on a total of 22 children including, 7 cases with acute glo- merulonephritis (A.G.N.), 6 with nephrotic syndrome (N.S.) and 9 with purpura nephritis (P.N.), and histological findings and depositions of fibrin (Fb), factor VIII-related antigen (VIIIR : AG), factor XIII subunit A (XIII. A) or factor XIII subunit S (XIII. S) in the glomerular lesion, were investigated in comparison with levels of fibrinogen (Fg), factor VIII and XIII in blood. In the acute stage of A.G.N., there was observed same evidence of mild glomerular capillary Fb. deposition, a companying deposition of VIIIR : AG, XIII A or XIII S, but depositions of VIII: AG and XIII A could not be found in the recovery or persistent stage. At the relapse phase of N.S., level of Fg., factor VIII and XIII in blood were elevated. But glomerular deposits of the coagulant factors were not detected in the cases with minimal change or mild proliferative lesion. On the other hand, intense depositions of Fb. and mild depositions of VIIIR : AG, XIIIR : AG, XIII A or XIII S were observed in the glomerular capillaries or mesangium area in nephritic nephrosis or frequent relapser. In P. N., there was seen an increased level of Fg. and a decreased level of factor XIII especially in the cases including severe proliferative glome rular lesion with crescent formation. In these cases, intense and dense deposit of Fb. was seen in glo merular capillaries and crescent, togather with mild to moderate deposition of VIIIR : AG, XIII A or XIII S in glomerular capillalies.

View full abstract

A 30-year old man developed chronic glomerulonephritis associated with hepatitis B. A renal biopsy revealed membranoprolif erative glomerulonephritis and immunof luorescence disclosed HBs-Ag in the glomeruli in a similar pattern to distribution of IgG and 1S1C. Remarkable findings, the electron microscopy study disclosed "fingerprint pattern" in the subendothelial and subepitherial deposits. A liver biopsy showed persistent hepatits. Laboratory data showed massive proteinuria, hypoproteinemia and hypercholesterolemia. Serum GOT, GPT was slightly eleveted but jaundice was not found. Serum HBs-Ag titer was remarkably elevated but HBs-Ab could not found. Circulating immune complexes could be detected by Clq deviation test. Serum Clq and C4 were slightly reduced, whereas the other comlement components were relatively normal. This case strongly suggested membranoproliferative glomrulonephritis which was induced by HBs-Ag.

View full abstract

A 55-year-old woman was admitted to our hospital because of muscle weakness and headache. She had long history of hypertension and albuminuria since age 38 when she had acute glomerulonephritis. On admission, blood pressure was 180/112mmHg. Laboratory data revealed Hb 9.9g/dl, serum Na 147mEq /1, serum K 2.3mEq/l, creatinine 2.8mg/dl. BUN 44.9mg/dl, GFR 16.7ml/min, PRA 0.34ng/ml/hr and aldosterone 95ng/dl. Adrenal scintillation scanning and adrenal phlebography suggested the evidence for the left adrenal adenoma. On February 8th. 1978, left adrenalectorny was performed. Tissue aldosterone level in adrenal adenoma revealed 7.8pg/g tissue. Histopathological findings of the left kidney showed marked arteriolosclerotic changes. After the operation her blood pressure, PRA and aldosterone level returned to normal range. To our knowledge this is the first case of successful adrenalectomy performed on a patient of primary aldosteronism with chronic renal failure in Japan.

View full abstract

1) Twenty-nine cases of renal diseases were administrated intravenously 30, 000 units/day of urokinase during 2 weeks. Urinary volume, urinary protein, urinary blood cells, blood urea nitrogen, serum creatinine, renal function, FDP in urine and blood, and fibrinogen in plasma before and after urokinase therapy were observed.2) Twelve cases were effective for urokinase therapy. GFR increased in 7 cases, urinary protein decr-eased in 10 cases and urinary red cells decreased in 5 cases.3) Eight cases in effective cases for urokinase therapy were taken renal biopsy. In these histological findings, 5 cases were proliferative glomerulonephritis, 2 cases were membranoproliferative glomerulon-ephritis and 1 case was membranonephropathy.4) In 2 cases of acute renal failure, after urokinase therapy GFR increased with diuresis. And, in pati-ents with pregnancy kidney, after urokinase therapy urinary protein and urinary blood cells decreased.5) In many cases that were effective for urokinase therapy, FDP in morning urine was positive. How ever, in chronic renal failure in which FDP in urine was posititve, urokinase therapy was non-effective.

View full abstract

This report consists of an autopsy case study of Potter's type I polycystic kidney in which the patient expired 15 minutes after the delivery due to respiratory distress. On the other hand the statistics of autopsy cases of polycystic kidneys in general among new born in our country seems to show a slight decrease of the incidence from the year 1973 up to now comparing with those in the years prior to that. The background and significance of the phenomenon seems to remain unknown likewise the knowledge whether it is also same in the type I polycystic kidneys partially because of the lack of more precise statistics of each type of the malformations. The authors therefore, discussed about the possibility to identify the type 1 polycystic kidneys from other types by the ordinal macroscopic and microscopic examinations of the kidneys to improve the above condition consulting with the previous reports by Osathanondh and Potter and Potter.

View full abstract

In our previous siudy, we reported about the impaired renal buffer action in hypoxia mainly due to the decreased ammonia excretion into the urine. In the present study, we investigated about ammoniagenesis and gluconeogenesis in renal cortical homogenate from the rats with control, hypoxia (10%O2+90% N2 gas inhalation), meta-bolic acidosis (HCl administration i.v.) and metabolic acidosis+hypoxia. In metabolic acidosis, ammonia production was increased to 180% and glucose production to 358% of control. On the contrary, ammonia production was decreased to 24%, and glucose production to 39% of control in hypoxia. Moreover ammonia production decreased to 39% and glucose production to 22% of acidosis in metabolic acidosis+hypoxia. When glutamine was added into the incubation medium, ammonia production increased in control, metabolic acidosis, and also in hypoxia and metabolic acidosis+hypoxia groups. Above-mentioned correlations were not found in liver homogenate. We concluded that the decreased urinary excretion of ammonia in hypoxia was due to the inability of the kidney to produce sufficient amount of ammonia associated with decreased gluconeogenesis.

View full abstract

In my previous studies, I reported about the impaired renal buffer action in hypoxia mainly due to the decreased ammonia excretion caused by the inability of the kidney to produce ammonia associated with decreased gluconeogenesis. In the present study, enzymatic activities on renal ammoniagenesis and gluconeogenesis were examined in renal cortical homogenate from rats with control, hypoxia (10%O₂+90% N₂ gas inhalation), metabolic acidosis (HC1 administration i.v.) and metabolic acidosis+hypoxia. Among these six enzymes measured, glutaminase, glutamic dehydrogenase, citrate condensing enzyme, phosphoenolpyruvate carboxykinase (PEPCK), fructose-1, 6-diphosphatase, and glucose-6-phosphatase, PEPCK activity was significantly increased by 400% of control in acidosis. On the contrary, in hypoxia PEPCK activity was decreased to 25% of control and in metabolic acidosis+ hypoxia to 6% of metabolic acidosis. No other enzyme activities were not well correlated to renal ammoniagenesis and gluconeo-genesis both in hypoxia and metabolic acidosis. Conclusion reached above mentioned study, I speculated that the inability of the kidney to produce ammonia and glucose in hypoxia was mainly due to the decreased activity of PEPCK.

View full abstract