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A 23-year-old woman presented with disturbance of consciousness and seizure. Her blood pressure was remarkably high, and brain magnetic resonance imaging (MRI) showed high-intensity T2 signals in the bilateral basal ganglia, corpus callosum, cerebral white matter, and cortex. With the administration of angiotensin II receptor blocker, the symptoms and MRI findings improved, along with normalization of blood pressure, and a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES) was made. Plasma renin activity was high, and the right kidney was severely atrophic. Results from renal and adrenal vein sampling revealed renal vascular hypertension derived from the right renal artery stenosis. The right kidney was then removed by laparoscopic nephrectomy. Pathological examination of the kidney confirmed the diagnosis of fibromuscular dysplasia (FMD). In juvenile-onset encephalitis/encephalopathy, PRES due to FMD should be included in the differential diagnosis.

We report a case of a 22-year-old male with juxtaglomerular cell tumor treated with laparoscopic partial nephrectomy. He was referred to our hospital with hypertension, high concentration of plasma renin activity (PRA) and renal mass. Dynamic enhanced computed tomography showed 17-mm weak contrast-enhancing tumor at the upper pole of the left kidney. Renin suppression and stimulation test revealed autonomous renin secretion although renal venous sampling failed to show significant difference in the PRA between the right and left renal vein. We performed laparoscopic left partial nephrectomy. The histological diagnosis was juxtaglomerular cell tumor. After the operation, his blood pressure and PRA were immediately normalized. Juxtaglomerular cell tumor is an important renal tumor as a curable cause of secondary hypertension.

Although hypokalemia is a common clinical problem, symptoms generally do not become manifest unless the serum potassium (K) falls rapidly. We encountered five cases with symptomatic severe hypokalemia (K<2.0 mEq/L) hospitalized for the past 15 months at our hospital. We examined the clinical characteristics and treatment of these patients. All five patients were women, and their mean age was 77.8 (73-82)years. They suffered from hypertension. Mean K level at admission was 1.66 (1.4-1.9) mEq/L and HCO3(-) was 48.3 (33.6-56.1) mmol/L. Plasma aldosterone level was low and plasma rennin activity was suppressed. All patients developed progressive muscle weakness with elevated creatinine phosphokinase. Three of the patients had received Chinese medicine which contained licorice, one received glycyrrhizin and the other one had received both. We diagnosed these cases as pseudoaldosteronism induced by glycyrrhizin. With discontinuation of the drugs and intravenous as well as oral K supplementation, serum K were normalized and clinical symptoms improved within 12 days. For one patient who developed cardiac dysfunction, concentrated K solution (230 mEq/L) was infused into the central vein. These findings show that glycyrrhizin ingestion should be kept in mind as a cause of an extreme degree of an hypokalemia, especially in elderly patients.

Discovery of (pro)renin receptor elucidated that prorenin is not only an inactive precursor of renin but also an endocrine hormone. The binding of prorenin to the (pro) renin receptor triggers two major pathways: the angiotensin II-dependent pathway as a result of nonproteolytic activation of prorenin, and the angiotensin II-independent, (pro)renin-receptor-dependent intracellular pathways. These two pathways of (pro)renin receptor significantly contribute to the development and progression of end organ damage in diabetes and hypertension. However, since renin is still active in the absence of the (pro)renin receptor, the contribution of (pro)renin receptor to the pathogenesis is reduced under conditions with high renin levels. Thus, assessment of the ratio of renin to prorenin is needed to evaluate the significance of (pro)renin receptor.

Primary aldosteronism (PA) is a form of surgically curable secondary hypertension. The prevalence of PA among hypertensive patients is reportedly between 5 and 15% and hypokalemia is rare in patients with PA. Therefore, hypertensives should be screened for PA. The aldosterone (PAC)-renin activity (PRA) ratio (ARR) has widely been used as the initial screening for PA; however, it is reported that the diagnosis of PA should not be based on the finding of a raised ARR. We compared the sensitivity and specificity of ARR for PA screening with those of PAC and PRA in 236 hypertensives, and ROC analysis revealed that PAC and PRA are more sensitive and specific than ARR for PA screening. The sensitivity and specificity of the captopril suppression test, furosemide plus upright test and ACTH stimulation test for secondary screening for PA were retrospectively examined in 94 patients with PA and 44 patients without PA. ROC analysis demonstrated that the ACTH stimulation test was the most sensitive and specific among these three tests. Therefore, we propose that hypertensives should initially be screened for PA using the criteria of PAC > or = 12.0 ng/dl and PRA < or = 1.0 ng/ml/h and should be secondarily screened using the ACTH stimulation test. Then ACTH-stimulated adrenal venous sampling should be performed in patients with the ratio of maximal PAC to cortisol after ACTH stimulation 0.85. Patients with unilateral secretion of aldosterone2 1400 ng/dl should undergo unilateral adrenalectomy and patients with bilateral secretion of aldosterone2 1400 ng/dl should be treated with antihypertensive agents.

In this study, we used alpha-human atrial natriuretic peptide (hANP) from staring on cardiopulmonary bypass and evaluated for the hemodynamics, ANP, renin activity, aldosterone, urine volume, glomerular filtration rate (GFR) and so on. The hANP decreased renin activity, aldosterone, systemic vascular resistance and increased urine volume, GFR and use of furosemide and KCL were decreased. We concluded that hANP was effective for hemodynamics, renal function and hormonal release on intra and post-operation in cardiac surgery, and low dose continuous infusion of alpha-hANP from staring on cardiopulmonary bypass will be expected as a newly application.

Extracorporeal shock wave lithotripsy (ESWL) is a safe and effective treatment for upper urinary tract stones. However, the mechanism by which this treatment may be involved in causing ventricular premature contractions (VPC) is unknown. We evaluated the relationship between VPC and plasma hormones in patients treated by ESWL. Holter monitoring was performed on 61 outpatients undergoing ESWL with electrocardiographic synchronization for upper urinary tract stones. The levels of cathecolamine, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and human atrial natriuretic peptide (hANP) were measured before, immediately after, and 7 days after ESWL. Systolic blood pressure increased significantly immediately after, and decreased 7 days after ESWL. VPC occurred during 23 treatments (37.7%) but during ESWL no significant relationship was observed with the treatment side or location. Epinephrine increased significantly immediately after ESWL. hANP increased significantly immediately after ESWL, and decreased 7 days later. VPC occurred in all patients who had an hANP value above 40 pg/ml before ESWL. These results suggest that VPC is related to hemodynamic changes, and that hANP can predict VPC during ESWL.

32 out of 83 in patients with atopic dermatitis showed a decrease of urine excretion during acute exacerbation and elevated levels of antidiuretic hormone (ADH 23 of 29 cases), renin (18 of 32 cases), angiotensin (22 of 29 cases) and aldosterone (16 of 37 cases). Six cases with high ADH showed severe pitting edema of lower legs with hypoalbuminemia. ADH, volume of urine and edema were improved when their skin symptoms subsided. There was no statistically significant relationship between the dose of steroid ointment and ADH. Also there was no correlation between low 17-OHCS or 17-KS and high ADH or renin.

A chronic model of hypertension, induced by continuous inhibition of nitric oxide synthase (NOS), was used to examine whether chronic NOS inhibition is associated with the heightened sympathetic activity and how nitric oxide (NO) produced by NOS contributes to maintain structural integrity of coronary artery and myocardial interstitium. Osmotic pumps were implanted intraperitoneally for 4 or 8 weeks to male Wistar rats. Solution in the osmotic pumps contained 0.2 M L-NG-nitroarginine methylester (LNAME) [low dose (LD)] or 1 M LNAME [high dose (HD)], or saline (SA). Sproke-prone spontaneous hypertensive rats (SHRSP) served as hypertensive controls. After 4 weeks the pumps in some rats were exchanged to the ones containing same solution (SA-SA, LD-LD, and HD-HD), or LNAME was discontinued and replaced by SA (LD-SA, and HD-SA). After 4 weeks, blood pressure (BP) of the LNAME-treated rats gradually rose from 112 to 142 (LD) and 180 (HD) mmHg. When the LNAME treatment was continued for the next 4 weeks, BP remained high (140 mmHg) in LD-LD. When LNAME was discontinued, BP returned to control levels (LD-SA: 110 mmHg; HD-SA: 122 mmHg). Heart rate (HR) decreased soon after initiation of the LNAME treatment, and remained lower in LD and LD-LD for 8 weeks, while it was gradually elevated and reached to the control level in HD. Discontinuation of the LNAME treatment normalized HR (LD-SA and HD-SA). Plasma dopamine levels were lower in the LNAME-treated rats and the withdrawal of LNAME normalized them. Plasma norepinephrine levels were significantly higher in HD than SA and LD, and it returned to control level in 8 weeks. Plasma renin concentrations were unchanged throughout the study. Microscopic examination (ME) revealed more severe thickening of coronary arterioles and fibrosis of myocardial interstitium in HD than in SHRSP. ME also revealed severe histiocyte infiltration in HD rats, while no kidney damages. These results suggest that, in the chronic model of hypertension induced by sustained LNAME administration, not only NO derived from endothelial NOS (NOS-3), but also the heightened sympathetic drive caused by central NOS (NOS-1) inhibition modifies progression of the disease. Furthermore, NOS-2 induced by histiocyte infiltration and its inhibition by LNAME may have resulted in the severe structural changes in the lesions. Thus, various NOSs may take part in maintaining cardiovascular integrity.

Blood pressure (BP), plasma active renin concentration (ARC), plasma renin activity (PRA), aldosterone (Aldo), atrial natriuretic peptide (HANP), plasma sodium (Na), plasma potassium (K), total protein (TP), hematocrit (Ht) and body weight (BW) have been measured in 101 patients, including 9 diabetic patients, undergoing hemodialysis for 5 through 278 months. BP, ARC, PRA and HANP correlated inversely with the duration of dialysis. Among 13 patients undergoing hemodialysis for more than 20 years, only one patient received antihypertensive drugs. This finding suggested that relative low ability of renin secretion and a slightly low concentration of HANP causes low blood pressure in long-term dialysis patients. ARC was significantly correlated with PRA, Aldo, Na, TP-A (TP concentration after hemodialysis), Ht(delta)% (difference between before and after hemodialysis) and BW(delta)%. These investigations suggest that the removal of large quantities of water and salt in each dialysis session may cause excessive secretion of renin. Though no relation was demonstrated between ARC and blood pressure in 101 patients, ARC was correlated significantly with blood pressure in 37 non-DM patients undergoing hemodialysis for less than 10 years and was inversely correlated in 55 non-DM patients undergoing hemodialysis for more than 10 years. Therefore, further analysis of other factors that maintain blood pressure, especially in long-term dialysis patients is required. Multiple regression analysis showed that major factors regulating the levels of blood pressure were duration of dialysis, Ht(delta)% and BW(delta)%. During dialysis, we observed significant correlation between ARC(delta)% and Ht(delta)%, but we did not find any correlation between the change in blood pressure and ARC. Furthermore, [correction of Forthermore] we found that caution should be paid to body water control especially in diabetic patients, because of their remarkable fall of BP during dialysis.

The effects of prostaglandin E1 (PGE1) on body temperature, catecholamines and stress hormones were evaluated in 10 patients undergoing elective prolonged surgery over 12 hours. PGE1 (0.03 microgram.kg-1.min-1) was administered in 5 patients and was not administered in 5 patients. Deep skin-surface temperature gradients were 5.1 +/- 2.3 degrees C in PGE1 non-administered group and 0.8 +/- 0.9 degree C in PGE1 administered group (P < 0.05). Pharyngeal-skin surface temperature gradients were 8.8 +/- 2.1 degrees C in PGE1 non-administered group and 1.5 +/- 1.5 degrees C in PGE1 administered group (P < 0.05). There were no significant differences between the two groups in respects to catecholamines, stress hormones, lactate level and blood sugar. PGE1 0.03 microgram.kg-1.min-1 is effective in maintaining peripheral circulation without causing body temperature changes during prolonged surgery.

The effects of cilazapril on exercise tolerance and neurohumoral factors were investigated in old myocardial infarction (OMI) patients with asymptomatic heart failure and reduced left ventricular ejection fraction. Cilazapril (0.5 mg) was administered once daily to OMI patients (n = 20) [NYHA class I, sinus rhythm, ejection fraction by radionuclide scanning < 50% (36.8 +/- 9.1%, mean +/- SD)]. Two weeks later, five patients were excluded from the study because of cough or hypotension, and 15 patients received 1.0 mg cilazapril once daily for the next 6 weeks. Exercise tolerance, neurohumoral factors and ejection fraction were measured in OMI patients before and after administration of cilazapril. Seven age-matched healthy adults served as the controls. OMI patients had latent heart failure because their exercise tolerance values and aldosterone levels were lower and alpha-atrial natriuretic polypeptide levels were higher than those in healthy subjects. In OMI patients, 8 weeks after cilazapril administration, exercise duration increased from 545 +/- 59 to 590 +/- 74 sec (p < 0.05), anaerobic threshold from 17.5 +/- 3.2 to 20.1 +/- 2.8 ml/min/kg (p < 0.05), peak-VO2 from 23.5 +/- 4.7 to 27.1 +/- 4.4 ml/min/kg (p < 0.05), plasma renin activity from 1.34 +/- 1.13 to 5.82 +/- 5.47 ng/ml/hr (p < 0.01) and alpha-atrial natriuretic polypeptide decreased from 100.7 +/- 44.3 to 80.5 +/- 28.0 pg/ml (p < 0.05). In patients with asymptomatic left ventricular dysfunction after myocardial infarction, 8 week's cilazapril administration improved exercise tolerance and neurohumoral conditions.

In order to clarify the relationship between vasoactive substances and changes in blood pressure (BP) during hemodialysis (HD) in patients with end-stage renal disease, we measured plasma renin activity (PRA), plasma concentration of aldosterone (PAC), and the plasma concentrations of epinephrine (E), norepinephrine (NE), dopamine (DA) and atrial natriuretic peptide (ANP) in patients on HD. Fourty-eight patients, consisting of 24 males and 24 females, were included in this study. Their mean age was 63.8 years, and their mean HD duration was 55.9 months. In 9 patients without diabetes mellitus (DM) and whose BP was stable during HD, PRA and plasma concentrations of E and NE increased significantly during HD, and that of DA decreased during HD. In 9 patients without DM and whose BP fell during HD, PRA and plasma concentrations of E and NE showed no significant response to the decrease in body weight during HD. In spite of the increase in NE concentration during HD in 8 patients without DM and whose BP was usually hypotensive, BP remained low. This might be due to the decrease in sensitivity of their peripheral autonomic receptors to NE. In the 9 patients with DM whose BP was stable and 13 patients with DM whose BP fell during HD, vasoactive substances made almost no effective response to the decrease in body weight during HD. In conclusion, we must take into consideration the fact that both hypotensive patients during HD and diabetic patients on HD might exhibit an abnormal response of their vasoactive substances.

Antihypertensive effects of repeated oral administration of cilnidipine in 2K1C renal hypertensive dogs were compared with those of nicardipine. On the first day, oral administration of cilnidipine (3 mg/kg) or nicardipine (3 mg/kg) markedly lowered both systolic and diastolic blood pressure 1 hr after administration. The hypotensive effects of cilnidipine were longer compared with those of nicardipine. Both drugs elevated the heart rate and plasma renin activity. On the 8th and 15th days, similar responses were obtained by repeated administrations of cilnidipine and nicardipine. After withdrawal of these drugs, no rebound phenomena in blood pressure were observed. The changes in mean blood pressure were correlated with plasma cilnidipine or nicardipine concentrations that were obtained at each time of blood pressure measurement (r = -0.598; P < 0.001 and r = -0.594; P < 0.001, respectively). These results suggest that stable and long-acting antihypertensive effects of cilnidipine for 15 consecutive days in renal hypertensive dogs are related to the change in plasma drug concentrations.

Effects of nicardipine on endocrine functions were evaluated in 10 surgical patients who received surgeries under total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK). Plasma levels of norepinephrine (NE), epinephrine (E), plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (hANP) were measured following nicardipine injection during 30 minutes of intraoperative hypertension. When the systemic blood pressure exceeded 160 mmHg systolic and 95 mmHg diastolic for five minutes, 0.5 mg approximately 10 mg of nicardipine was administered for 30 minutes to maintain the systolic blood pressure below 160 mmHg. Following the injection of nicardipine a significant reduction by 20% in the mean systolic and diastolic pressure was observed. Mean heart rate increased by 5%, but the increase was not significant. Plasma NE increased significantly 1.7 time from the control level at 15 minute following the injection. Plasma levels of E, PRA, aldosterone and hANP showed no significant changes.

A 2-month-old girl having a left multicystic dysplastic kidney with contralateral mild hydronephrosis is described. Furosemide was administered orally because of hyperpotassemia during the period between 1 month and 7 months of age. Peripheral plasma renin activity and plasma aldosterone activity increased at the age of 6 months, and ultimately reached the peak at 9 days after discontinuation of furosemide at the age of 7 months. Peripheral plasma renin activity and plasma aldosterone activity were normalized at the age of 11 months. Blood pressure during the whole period was normal. Contralateral hydronephrosis was improved gradually. The level of serum creatinine became normal at the age of 50 days. A case with a high level of plasma renin and aldosterone activity temporarily induced by furosemide was reported. Pathophysiology of pseudo-Bartter syndrome without hypopotassemia due to furosemide is discussed.

The effects of the bathing on short-term and ciracadian blood pressure (BP) in bedridden elderly patients were investigated in 10 bedridden patients (4 male: 6 female) living in a community home. The mean age of the subjects was 78.7 years old and causes of bedridden status were cerebrovascular disease in 9 and spinal damage in one. To study the short-term hemodynamic effect of bathing, BP and pulse rate were measured every 2 minutes from 10 minutes before bathing to 14 minutes after. Blood samples were collected before and after bathing for measurements of plasma catecholamine and plasma renin activity. To study the effect of warm bathing on circadian, BP, ambulatory BP was non-invasively monitored every 15 minutes for 24 hours on days with and without bathing. In the short-term phase, BP temporally elevated when washing the body outside the bathtub accompanied with a decline soaking in warm water (38 degrees C). Plasma catecholamine did not change after warm bathing. In the study of circadian change of BP, systolic BP on days of warm bathing remained at a lower level for 12 hours after bathing compared to days without bathing. In conclusion, hypotensive effects after bathing were prolonged in the bedridden elderly patients.

A total of 70 patients with renal trauma were treated at the Department of Urology, Nara Medical University and Nara Prefectural Hospital, including Life-Saving Emergency center, from January 1982 to June 1993. They were between 3 and 79 years old (mean 30.0) and preponded to the younger generation. The main cause of injury was traffic accident in 46 cases (65.7%). According to the Classification of Renal Injury by the Japanese Association for the Surgery of Trauma in Japan, there were 31 cases (44.3%) of type I (subcapsular injury), 18 cases (25.7%) of type II (superficial injury), 15 cases (21.4%) of type III (deep injury), and 6 cases (8.6%) of type IV (pedicle injury). Surgical treatment was performed in 17 cases (24.2%). The major associated injuries were bone fracture in 32 cases (45.7%), lung injury in 17 cases (24.2%), and liver injury in 15 cases (21.4%). Furthermore, hydronephrosis and ureteral tumors were incidentally found in 4 and 1 patient during the course of treatment for renal trauma. Post-traumatic plasma renin activities (PRA) in types III and IV were significantly higher than those in types I and II. Hypertension developed in 1 case of types I and II and 4 cases of types III and IV. The mean level of PRA was significantly decreased 2 years after renal injury in both groups. We should bear in mind that renal trauma may be associated with other urological diseases such as hydronephrosis and urological malignancies, and post-traumatic PRA should be followed carefully.

A schizophrenic woman, aged 45, was admitted complaining of high fever, oliguria, blackish urine, muscle swelling and pain. She had been treated for the past 3 years with haloperidol (8 mg), levomepromazine (150 mg), chlorpromazine (75 mg), lithium carbonate (600 mg), bromocriptine mesilate (7.5 mg), etizolam (1 mg), and flunitrazepam (2 mg), Physical examination revealed her to be an obese and uncommunicatable woman with swelling and weakness of the extremities and abdominal distension without borborygmus. Urine was dark brown and (+) for protein and occult blood. Blood chemistry analysis revealed BUN 71 mg/dl, creatinine 6.8 mg/dl, CPK 143,850 IU and myoglobin 3,980 ng/ml. PRA on the 11th hospital day was 96 ng/ml/hour. This patient fulfilled the Levenson's diagnostic criteria for manifestations of neuroleptic malignant syndrome (NMS). High PRA did not decrease after cessation of the diuretics. After treatment with dantrolene sodium and 10 treatments with hemodialysis, azotemia disappeared with the start of diuresis. The PRA also decreased to the normal level. Characteristic acceleration of the central sympathetic stimuli in NMS seemed to have induced hyperreninemia, which together with rhabdomyolysis, might have contributed to the development of acute renal failure.

Hyporeninemic hypoaldosteronism has mainly been described in patients with diabetes mellitus. In order to elucidate the mechanisms of hyporeninemia in diabetic patients, the author studied the response of active renin concentration (ARC) and inactive renin concentration (IRC) to the administration of captopril or sodium depletion in patients with diabetes mellitus and glomerulonephritis and in normal subjects. The diabetic patients were separated into four groups: Group 0, diabetic patients without neuropathy or nephropathy; Group I, those with neuropathy without nephropathy; Group II, those without neuropathy with nephropathy; Group III, those with neuropathy and nephropathy. Diabetic patients with some complications had slightly lower plasma active renin levels than those without complications. The mean increase in plasma active renin after captopril (delta ARC) and sodium depletion was lower in group I than in group 0, and there was no difference between group II and group 0. There was no correlation between delta ARC and creatinine clearance (Ccr) in diabetes mellitus. Plasma prorenin was higher in group I than in group 0, and there was no difference between group II and group 0. No significant change of prorenin after captopril was observed in all groups, but the mean increase in plasma inactive renin after sodium depletion was slightly higher in groups I and III than in groups 0 and II. ARC/IRC was significantly lower in group I than in group 0, and there was no difference between group II and group 0. There was no correlation between ARC/IRC and Ccr in diabetes mellitus, but significant correlation between ARC/IRC and postural change in systolic blood pressure. In three diabetic patients with hyporeninemic hypoaldosteronism, the postural fall in systolic blood pressure was significant, and ARC/IRC was significantly low, but IRC was not high. These results suggest that autonomic dysfunction is a major factor in an impairment of the processing of prorenin to active renin in diabetic patients, and severe autonomic dysfunction may impair the biosynthesis of prorenin in patients with hyporeninemic hypoaldosteronism.

A case of Ask-Upmark kidney is presented. An 18-year-old male patient referred to this facility presented with symptoms of hypertension, microscopic hematuria and proteinuria. A hormonal study revealed a high plasma renin activity level. Intravenous pyelography and abdominal computed tomography revealed thinning of the cortex with calyceal dilatation. Arteriography revealed a deep cortical groove in the middle portion of the kidney without renal arterial stenosis. Plasma renin activity of the left renal vein was significantly higher than that of the right renal vein. A left simple nephrectomy was performed under the diagnosis of Ask-Upmark kidney. Postoperatively, plasma renin activity returned to the normal range and a decrease in blood pressure was noted. Recent reports have suggested Ask-Upmark kidney to be a consequence of vesicoureteral reflux rather than a true congenital malformation. Our case indicated no evidence of vesicoureteral reflux and suggests that the lesion was congenital rather than acquired.

We report a 54-year old man diagnosed as idiopathic hyperaldosteronism (IHA) at least 12 years after the onset. At the age of 42, he showed hypertension (162/100mmHg), hypokalemia, metabolic alkalosis, low plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) in a supine posture. Both PRA and PAC were elevated after a 2-hour ambulation following furosemide (60mg) injection. Since the accumulation of radioactivity following 131I-aldosterol injection with combined administration of dexamethasone was equally detected in both adrenal areas, he was diagnosed as low-renin essential hypertension (LREH). Blood pressure (BP) decreased to the normal range after treatment with nifedipine (40mg/day). At the age of 47, however, BP was hypertensive (164/106mmHg) serum potassium (K) level was normal. Although PAC was normal in a supine posture, it increased after a 2-hour ambulation following furosemide (60mg) injection. PRA after the stimulation was still suppressed despite the increase in PAC. At the age of 54, BP was 172/94mmHg. Serum K level was 3.4mEq/L. PRA was suppressed below 0.1 ng/ml/hr, while PAC was above the normal range (170pg/ml) in a supine posture. Serum cortisol and urinary excretion of 17-OHCS and 17-KS were within normal limits. PRA was still suppressed below 0.1 ng/ml/hr after a 2-hour ambulation following furosemide (60mg) injection, but PAC was markedly increased (330pg/ml). There was a diurnal rhythm of aldosterone, which was parallel to that of ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

To elucidate the effects of exercise in water on the maternal circulation, twenty normal pregnancies were examined under the following three conditions; 1) on the land at rest, 2) during water immersion and 3) after the exercise in water. Their gestational ages were from 25 to 37 weeks (31 +/- 4 weeks, mean +/- S.D., n = 20). We examined the blood pressure, the urine volume throughout the examination, CBC and the levels of vasopressin, plasma renin activity and human atrial natriuretic peptide (hANP). The blood volume calculated from the Hb and Ht were significantly (p < 0.001) increased during the water immersion (105.8 +/- 2.5%), even after the exercise (101.6 +/- 2.9%). Vasopressin was decreased during the water immersion and increased after the exercise, but plasma renin activity was decreased in these two conditions. The hANP concentration was significantly (p < 0.001) increased after the exercise in water and correlated with the urine volume (ml/hour) during the examination. These results show that the decline in blood pressure and the increase in the urine volume during the maternal swimming were caused by the decreased plasma renin activity and the increased hANP concentration resulted from the blood volume expansion during the exercise in water.

In 30-40% of patients with primary aldosteronism owing to adenoma, hypertension is not relieved even though a hyper-functioning adenoma has been completely removed. The purpose of this study is to determine whether the prognosis of hypertension can be evaluated pre-operatively in patients with primary aldosteronism. Thirteen patients (6 men, 7 women; 47 +/- 9 years old) with primary aldosteronism were studied and adrenalectomy was performed in all cases. The success of the operation was confirmed by the normalization of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and serum potassium. Eight patients, 3 men and 5 women, whose blood pressure (BP) was reduced to below 140mmHg systolic and 90mmHg diastolic at one year after the operation were classified as "group N" and the other 5 cases, 3 men and 2 women, remained hypertensive and were classified as "group H". There were no significant differences in the age of the patients, duration of hypertension, pretreatment mean BP and severity of hypertension between the two groups. Thus, it is doubtful that the lack of improvement of hypertension is due to the irreversible damage of the small arteries. Although pretreatment BP was similar in the two groups, systolic BP after the administration of 200mg per day of spironolactone for one week was significantly reduced in group N, but not in group H. Moreover, a significant correlation was found between mean BP after treatment with spironolactone and post-operative mean BP in all subjects. Pretreatment PRA was significantly lower in group H.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of human chorionic gonadotropin (HCG) on renin concentration and renin mRNA was studied using the testis and kidney of rats. Forty-five rats were divided into three groups. The first group (25 rats) was used for short time course study with single injection of 150 IU HCG and the second group (10 rats) for long term injection of 150 IU HCG daily for 3 weeks. In both groups, serum and testicular sample were taken after 24 hours both nephrectomy in order to exclude the influence of renal renin and angiotensin. The third group (10 rats) was used to find the effect of HCG on renal renin. Plasma and testicular renin concentration were measured by radioimmunoassay of angiotensin I. The specificity of renin concentration was determined using a specific renin antibody. Renin mRNA of the kidney and testis were measured by a sensitive RNAase protection assay method. Testicular renin mRNA increased and reached the maximum level at 8 hrs after 150 IU HCG single injection. And also testicular renin concentration significantly increased and it showed the maximum levels at day 3. However long term HCG administration in rats showed higher in levels in testicular renin concentration, however renin mRNA level was not increased. Non-nephrectomized rats showed low levels of plasma renin concentration and no changes in mRNA after HCG administration. The results suggest that renin angiotensin results suggest that renin angiotensin system independently exists in the testis and testicular renin mRNA is increased by HCG administration.

Recent reports have shown the existence of renin in Leydig cells of the rat testis and immunoreactive renin activity in the human testis. But we could not rule out the possibility that the renin found in the testis is contamination of plasma components by endocytosis. In the present study we tried to demonstrate the renin production in the human testis by the following experiments. At first, we measured the plasma renin activity and testosterone in the internal spermatic vein simultaneously after treatment with hCG and obtained the results that suggested hCG-induced renin secretion in the human testis. Next, we showed the hCG-dependent renin production from the cultured human Leydig cell tumors in vitro. Thirdly, we demonstrated the existence of renin mRNA in the human testisusing reverse transcriptase-polymerase chain reaction (RT-PCR). Fourthly, we detected significant signals of human renin mRNA in the human testicular tissues by in situ hybridization. From the above results, it was demonstrated that the human renin gene was hCG-dependently expressed in the human testis.

Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p < 0.01 and p < 0.05, respectively) in the patients with Basedow's disease than in the normal subjects, whereas basal PA level was similar in the two groups. The ACTH injection induced similar increases in plasma cortisol, plasma 18-hydroxycorticosterone (18-OHB) and PA in the two groups. The graded AII infusions also produced increases in plasma 18-OHB and PA in the two groups. Responses of these two corticosteroids to AII were, however, significantly lower (p < 0.05) in the patients with Basedow's disease than in the normal subjects. In the experimental animal study, basal PRA levels and the adrenal glomerulosa cell count/adrenal were significantly higher (p < 0.05) in the H-rats than in the control rats, whereas basal PA levels were similar in the two groups. Aldosterone production in response to AII, ACTH, and potassium increased in a dose-dependent manner in the two groups. Responses of aldosterone production to AII were, however, significantly lower (p < 0.05) in the H-rats than in the control rats. These results suggest that the impaired responsiveness of adrenal zona glomerulosa cells to AII, as well as an increased metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.

Recent increased use of ultrasonography and computed tomography (CT) has detected a substantial number of incidentally discovered adrenal tumor (incidentaloma). In our institute the discovery rate of adrenal incidentaloma per number of abdominal CT examinations was 0.43%. Those incidentalomas were incidentally found during examination for abdominal discomfort and lumbar pains or evaluation of the cause of hypertension. In the group study by the research committee on "Disorders of Adrenal Steroid Hormones" under the sponsorship of the Ministry of Health and Welfare of Japan, in 53 of 149 patients with incidentaloma, surgical resection was done during 5 years between 1983 and 1989. The pathological examination of those tumors revealed 67.9% of non-hyperfunctioning adrenocortical adenoma, 9.4% of adrenal cancer, 9.4% of ganglioneuroma, 5.7% of pheochromocytoma, 5.7% of adrenal cyst and 1.9% of myelolipoma. The criteria for resection of adrenal incidentaloma have not been established. However, tumors having a diameter of over 5 cm are generally excised in most institutes. Tumors having a diameter of between 3 cm and 5 cm are usually resected if the shape of the tumor is ambiguous and the margin of the tumor is irregular. Tumors having a diameter of less than 3 cm should be carefully followed up by abdominal CT examination every 6 months.

Digitalis glycosides are the first-choice drugs in the treatment of the patients with congestive heart failure and atrial fibrillation. Recently, it has been shown that digitalis glycosides have potentially beneficial neurohumoral modulating effects by decreasing excessive neurohumoral responses directly or by improving baroreflex mechanisms in congestive heart failure. Accordingly, there are many investigators who believe that digitalis glycosides are neurohormonal modulating agents in heart failure. There may be a dissociation between hemodynamic and neurohormonal effects in response to digitalis glycosides. The activation of the neurohormonal system may be present in patients with asymptomatic left ventricular dysfunction. Digitalis glycosides may therefore be used, not only to improve symptomatic congestive heart failure, but also to protect against the progressive deterioration of asymptomatic cardiac dysfunction.

Although various mediators such as platelet activating factor, anaphylatoxin and cytokines are considered to be involved in the pathology of endotoxin-induced shock, an endothelium-derived relaxing factor (EDRF), nitric oxide (NO) or its related substance, has recently been shown as a vasodilating factor that is produced from L-arginine. On the other hand, NG-nitro-L-arginine (L-NNA) is shown to inhibit NO production from L-arginine. Thus, in order to examine a possible involvement of NO in the shock, the effect of L-NNA administration was studied on the hemodynamics and plasma hormone levels during endotoxin-induced shock in anesthetized dogs. Twenty-five mongrel dogs were divided into the following 5 groups; (1) In group C, only physiological saline was administered. (2) In group L, a bolus injection of L-NNA (4 mg/kg B.W.) was followed by a continuous infusion of the agent (0.05 mg/kg B.W./min) for 120 min. (3) In group E, lipopolysaccharide (LPS) E. Coli 011:B4 2.625 mg/kg body weight was administered. (4) In group LE, L-NNA administration (bolus and continuous) the same as in group L was started 5 min before the injection of LPS. (5) In group EL, L-NNA administration (bolus and continuous) was started 5 min after the injection of LPS. In Group LE, MAP decreased to -45.9 mmHg 5 min after LPS injection and -33.0 mmHg 120 min from pre-level. The levels of MAP from 15 to 90 min were significantly higher than those in Group E. In Group EL, MAP decreased to -61.4 mmHg 5 min after LPS injection and this low level (-59.5 mmHg) continued for 120 min. A protecting effect of L-NNA against LPS-induced hypotension was clearly observed only when administration of the agent was started before LPS injection. These results indicated that LPS induced shock could be produced by a possible increase of NO production in the vascular endothelial cells. The other finding in the present experiment using anesthetized animals was that L-NNA had a stimulatory action on some endocrine systems such as the renin-aldosterone system and pituitary-adrenal axis, although the exact mechanism of this action of L-NNA on such systems was unclear.

We investigated the correlation between aging and sensitivity of blood pressure to salt. 88 non-treated essential hypertensives were divided into four groups: less than 40 years old (n = 20), 40-49 years old (n = 20), 50-59 years old (n = 39), and greater than 60 years old (n = 11). Changes of blood pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma norepinephrine (PNE), and plasma epinephrine (PE) due to salt load were compared among four groups. Salt sensitivity of blood pressure was increased with aging, and there was a positive correlation between them (r = 0.30, p < 0.01). Decrement of PRA due to salt load was decreased with aging, and there was a negative correlation between them (r = -0.35, p < 0.05). PCA and PNE were suppressed by salt load, and the decrement degrees did not change with age. PE did not change by salt load. We conclude that salt sensitivity is increased with age in essential hypertensives, and renin-angiotensin system might be involved in it.