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We report here a case of Sipple's syndrome, and we also analyze the relationship between the type of hypertension and urinary excretion of catecholamines in Sipple's syndrome based on the literature in Japan. One hundred and fourteen cases of Sipple's syndrome have been reported in Japan. The hypertension of patients with Sipple's syndrome shows a ratio of fitfull hypertension to continual hypertension of 6 to 1, whereas the ratio is 1 to 1.5 in patients whose pheochromocytoma is not accompanied by Sipple's syndrome. The patients with Sipple's syndrome, being pheochromocytoma can be classified into the adrenaline (U-AD) dominant type and noradrenaline (U-NA) dominant type based on the catecholamine excretion in the urine. The U-AD predominant (U-AD/U-NA greater than 0.4) patients mostly reveal fitfull hypertension, while patients with continual hypertension hardly show U-AD predominant.

Low doses (10(-16)-10(-10) M) of endothelin-3 (ET-3) elicited continuous vasodilations of mesenteric arteries preconstricted with norepinephrine (NE) but not with KCl. In arteries perfused with Ca2+ free solution, ET-3 did not affect the perfusion pressure. In endothelium-denuded arteries preconstricted with NE, ET-3 significantly elevated the perfusion pressure in a dose-related manner. The levels of cyclic GMP and cyclic AMP from the intact arteries were significantly elevated by ET-3; the cyclic GMP elevasion disappeared with methylene blue. Following endothelium-denudation, cyclic GMP elevation was abolished, but cyclic AMP elevation was unaffected. Levels of 6-Keto-PGF1 alpha in the arteries were not changed appreciably by ET-3. These data indicate that the vasodilating effects of ET-3 depend on the presence of extracellular Ca2+ and the existence of endothelium. They are accompanied by elevations of cyclic nucleotides and the elevation of cyclic GMP depends on the endothelium. It is possible that the vasodilating effects of low doses of ET-3 are associated with endothelium-derived relaxing factor.

The ability of immune complexes (IC) derived from rat renal tubular epithelial (RTE) antigen to trigger the production of interleukin-1 (IL-1) was investigated. When cultured rat mesangial cells (MC) were activated by the IC, substantial amounts of IL-1 could be detected in the culture supernatants as measured by the mouse thymocyte assay. To avoid the effect of prostaglandins on the IL-1 assay, we cultured the MC with addition of indomethacin and assayed IL-1 activity in the culture supernatants. This cyclooxygenase inhibitor augmented IC-induced IL-1 production. These biological activities were neutralized by a specific antibody to IL-1. These findings suggest that IC may participate in local inflammatory responses in the kidney partly due to their capacity to induce the synthesis of MC IL-1.

We examined the effect of endothelin-3 (ET-3) at a high dose (pressor dose) and a low dose (non-pressor dose) in rat perfused kidney (PK), since ET-3 has recently been reported to exert a vasodilator action especially at a low dose. Kidneys were perfused with Krebs-Henseleit buffer at a fixed flow rate (6 ml/min) in situ. After collection of the renal venous effluent and urine for 20 min, vehicle (saline; n = 6), 10(-13)M ET-3 (low dose; n = 6) or 10(-8) M ET-3 (high dose; n = 6) was added to the perfusate, and sample collection was performed for the same period with each. The high dose of ET-3 significantly increased the perfusion pressure, fractional sodium excretion and synthesis of prostaglandins (PGs) consistently with a significant reduction in the glomerular filtration rate (GFR). On the other hand, the low dose of ET-3 significantly increased the GFR, urine volume and free-water clearance with no change in the perfusion pressure or synthesis of PGs. These findings suggest that a low dose of ET-3 can increase the glomerular capillary ultrafiltration coefficient and that ET-3 exerts an influence on sodium and water handing in the rat PK.

We have reported that low doses of endothelin-3 (ET-3) elicited continuous vasodilation of rat mesenteric arteries, which is possibly related to endothelium-derived relaxing factor (EDRF). In order to clarify whether or not the vasodilating effects of ET-3 are associated with EDRF, we examined the effects of L-NG-monomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced vasodilation of rat mesente-Hc arteries. Infusion of 50 microM L-NMMA inhibited the vasodilation induced by 10(-13) M ET-3 and rather elicited an increase in perfusion pressure, which itself was decreased by infusion of 150 microM L-arginine. In the presence of 50 microM L-NMMA, 10(-13) M ET-3 did not elicit any vasodilation of the mesenteric arteries preconstricted with NE, in which 150 microM L-arginine, but not D-arginine, caused considerable vasodilation. These data suggest that the vasodilating effects of low doses of ET-3 are associated with EDRF as an endothelium-derived nitric oxide.

It has been demonstrated that the adenylate cyclase activity of vascular smooth muscle regulates its tonus. The present study was undertaken to examine adenylate cyclase activity in early and established deoxycorticosterone acetate (DOCA)/salt hypertensive rats. Early and established DOCA/salt hypertensive rats were prepared by injecting 30 mg of DOCA weekly for 3 and 10 weeks, respectively, into male Wistar rats given drinking water with l% saline. The membrane protein fraction of the aorta was obtained by centrifugation at 37, 000 g. To the incubation medium containing the protein, 50μM isoproterenol, 100μM GTP, 50μM forskolin or 25μM calmodulin was applied. The adenylate cyclase activity was determined by a modified method developed in our laboratory using double. isotope counting. The adenylate cyclase activity in the early DOCA/salt hypertensive rats was significantly higher (p < 0.05) than that in the control rats in the basal condition, which was unaffected by additions of isoproterenol, GTP or forskolin. There was no significant difference in basal adenylate cyclase activity between the established DOCA/salt hypertensive and control rats. The adenylate cyclase activities in the established DOCA/salt hypertensive rats were significantly lower with GTP (p < 0.02) and forskolin (p < 0.01) as compared with the control rats. Calmodulin elevated the adenylate cyclase activity significantly (p < 0.05) in the established DOCA/salt hypertensive rats as well as in the control rats. However, enzyme activity with calmodulin in the established DOCA/salt hypertensive rats was significantly lower (p < 0.05) than that in the control rats. These results suggest that the adenylate cyclase activity of vascular smooth muscle in early DOCA/salt hypertension was fully stimulated in the basal condition, and that there was an abnormality distal to the β-adrenoceptor, especially the catalytic subunit of the adenylate cyclase in established DOCA/ salt hypertension. Accordingly, it is thought that reduction of the enzyme activity may be attributable in part, to biochemical events involved in the pathogenesis of DOCA/salt hypertension.

We examined the effect of angiotensin I (AI), without the effect of angiotensin II (AII) converted from AI, on the weight of the adrenal glands, adrenal corticosterone (B) and adrenal aldosterone under conditions where the renin-angiotensin system was suppressed, since a reduction in the size of the adrenal glands is often observed in DOCA/salt hypertensive rats. Sixty male Wistar rats fed on a 1% NaCl solution were divided into 6 groups as follows: a) Salt group: received sesame oil and vehicle, b) Salt + C group: received sesame oil and MK422 (0.14 mg/day), an angiotensin converting enzyme inhibitor (CEI), c) DOCA group: received DOCA (30 mg/week) and vehicle, d) DOCA + A group: received DOCA and AI (0.5 mg/kg/day), e) DOCA + A + C group: received DOCA and AI with MK422, and f) DOCA + C group: received DOCA and MK422. After 4 weeks, the rats were sacrificed to sample their blood and remove their adrenal glands. There was no significant difference in adrenal B among the groups apart from the DOCA + C group. Adrenal aldosterone was lower in the groups of DOCA/salt hypertensive rats than in the Salt group and Salt + C group. Furthermore, the DOCA + A + C group and DOCA + C group had lower adrenal aldosterone levels than the DOCA group and DOCA + A group.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the contribution of L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF) on vascular cyclic GMP formation, we examined the effects of L-NG-monomethyl arginine (L-NMMA), and analog of L-arginine, on basal and acetylcholine (ACh)-, sodium nitroprusside (SNP)- and atrial natriuretic peptide (ANP)-induced cyclic GMP formations in rat mesenteric arteries. The mesenteric arteries were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the arteries were collected before and after infusions of graded doses of ACh, SNP or ANP in the absence or presence of 100 microM L-NMMA, and the levels of cyclic GMP were measured. Basal and ACh-induced cyclic GMP formations in the mesenteric arteries were significantly inhibited in the presence of L-NMMA, whereas a concomitant infusion of 300 microM L-arginine restored the inhibition of basal as well as ACh-induced cyclic GMP formations. L-NMMA did not affect SNP- and ANP-stimulated cyclic GMP formations, respectively. These results suggest that L-arginine is necessary for not only the stimulated cyclic GMP formation but also the basal cyclic GMP formation in the mesenteric arteries, whereas the SNP- and ANP-stimulated cyclic GMP formations in the arteries are independent of L-arginine.

We investigated the basal levels and responses of cyclic GMP (cGMP) derived from perfused mesenteric arteries to acetylcholine (ACh) and sodium nitroprusside (SNP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) at different ages, in order to evaluate the basal and stimulated release of endothelium-derived relaxing factor (EDRF) from the resistance vessel during the development of hypertension. The mesenteric arteries were removed from 8-, 12- and 20-week-old WKY and SHR, and were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the perfused arteries were corrected before and after infusions of graded doses of ACh or SNP, and the levels of cGMP were measured. The basal levels of cGMP from the msenteric arteries in the 12- and 20-week-old SHR were significantly lower than those in age-matched WKY. A negative correlation was observed between the basal levels of cGMP and the systolic blood pressure in SHR, but not in WKY, among all ages. On the other hand, there were no differences in the responses of cGMP to infusion of ACh between the WKY and SHR at each age. Moreover, the responsiveness of cGMP to in-fusion of SNP in the 12-week-old SHR was much higher than that in age-matched WKY. These data suggest that the basal cGMP formation in the arteries which may reflect the basal release of EDRF is reduced in older SHR and is associated with the development of hypertension, and that the stimulated ralease of EDRF is not associated with the development of hypertension.

We studied, prospectively, the predictive value of late potentials to cardiac sudden death and sustained ventricular tachycardias in 385 patients with myocardial infarction surviving over 4 weeks. Signal averaged electrocardiogram was performed over a 4 week period from the onset of acute myocardial infarction in all patients. Late potentials were observed in 118 of 385 patients. During the mean follow up period of 24.3 months, 17 patients had cardiac sudden death and 15 patients had symptomatic sustained ventricular tachycardias. In 16 of 17 patients with cardiac sudden death and 14 of 15 patients with sustained ventricular tachycardias, late potentials were observed. Sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy of late potentials to cardiac sudden death in these 385 patients were 94.1%, 72.3%, 13.6%, 99.6% and 73.2% respectively. Also, these predictive values of late potentials to sustained ventricular tachycardias in the group of patients were 93.3%, 71.9%, 11.9%, 99.6% and 72.7%, respectively. We concluded that the clinical usefulness of late potentials in patients with myocardial infarction surviving over 4 weeks in the negative predictive value to cardiac sudden death and sustained ventricular tachycardias is superior to that of positive predictive value. Sensitivity of late potentials to these events is also higher.

The effect of atrial natriuretic peptide (ANP) on adrenal renin and aldosterone was investigated in anesthetized rats. Under pentobarbital anesthesia 40 mg/kg), intravenous infusion of ANP (0.25 micrograms/kg/min) for 45 min failed to alter the adrenal renin, adrenal aldosterone, and plasma aldosterone (PA). In this condition, intraperitoneal injection of ACTH (10 micrograms/kg) significantly increased the adrenal renin (from 2.4 +/- 0.1 to 5.0 +/- 0.08 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 13.6 +/- 1.3 to 22.7 +/- 2.3 ng/mg protein, P less than 0.01) and PA (from 59.8 +/- 5.8 to 75.5 +/- 7.4 ng/dl, P less than 0.05), respectively. Under ACTH stimulation, ANP infusion induced significant decreases in adrenal renin (from 5.0 +/- 0.08 to 2.8 +/- 0.2 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 22.7 +/- 2.3 to 16.2 +/- 1.8 ng/mg protein, P less than 0.05) and PA (from 75.5 +/- 7.4 to 61.6 +/- 4.9 ng/dl). These results suggest a possible role for adrenal renin in the mechanism underlying the inhibitory effect of ANP on aldosterone production in vivo.

In the present study, hog pancreatic kallikrein (HPK, 2,000 KU/kg body weight) was intramuscularly injected into male rabbits and several plasma hormones [kinin, prostaglandin E (PGE), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TXB2), plasma renin activity (PRA), aldosterone, and ACTH] were measured before and after the HPK administration, in order to clarify the role of glandular kallikrein in the blood. The plasma kinin concentrations were significantly (p less than 0.001) increased from 1 +/- 1 (mean +/- SE), the baseline level, to 230 +/- 22, 288 +/- 36 and 130 +/- 9 pg/ml at 30, 60, and 120 min, respectively, after HPK administration. The plasma level of PGE were slightly increased after HPK administration, but the change was not significant compared to the mean baseline level. The plasma levels of 6-keto-PGF1 alpha were significantly increased from 229 +/- 38, the baseline level, to 594 +/- 131 (p less than 0.05) at 30 min after the administration of HPK and tended to increase (378 +/- 67) at 60 min after the HPK administration, but fell to 278 +/- 37 pg/ml at 120 min after the administration of HPK. On the other hand, the changes in plasma TXB2, aldosterone, ACTH, and PRA before and after HPK administration were not significant. The present results showed that exogenous intramuscular administration of HPK increased the plasma levels of kinin and prostacyclin, but caused no elevation in the plasma levels of other hormones including PRA. It is concluded, therefore, that in this acute experiment, there was a close relationship between the kallikrein-kinin system and prostaglandins.

A 29-year-old Japanese male with a 19-year history of subcutaneous eosinophilic lymphoid granuloma (Kimura's disease) was referred to the Nephrology Service of the Nihon University Hospital for evaluation of edema and massive proteinuria. The renal biopsy disclosed minimal glomerular lesions. In this paper a case of nephrotic syndrome associated with eosinophilic lymphoid granuloma is reported.

IZUMI, Y., HONDA, M., HATANO, M. and KAWAHARA, Y. Influence of Food on the Clinical Effect of Angiotensin I Converting Enzyme Inhibitor (SQ 14, 225). Tohoku J. exp. Med., 1983, 139 (3), 279-286 -In order to clarify the influence of food on the clinical effect of angiotensin I converting enzyme inhibitor (SQ 14, 225, captopril), 25mg of the drug was administered to patients with hypertension using in a two-way crossover study design. In the first study (study I), each subject received the drug 30min after breakfast, and changes in blood pressure (BP), blood concentration of captopril (BCC), plasma renin activity (PRA), plasma aldosterone (PA) and plasma angiotensin I converting enzyme activity (ACE-A) were determined for 3 hr. BP was recorded for 6 hr. Four days after study I, the same subjects received the drug 2hr after breakfast, and each parameter was again determined (study II), similarly to study I. No significant difference in the hypotensive responses to captopril was observed between both studies during 6hr of observation. Maximum hypotensive effects were found within 90min of the treatments in study I and study II, and BP returned almost to baseline levels at 6 hr in both studies. Maximum BCC levels were found 60 and 90min after the drug administration in studies I and II, respectively, and these approximated to half of each maximum level at 180min. There were no statistically significant differences in the biological half-life (T1/2), maximum concentration (C max), maximum concentration time (T max), and area under the blood concentration curve [AUC]03 between both studies. The peak in PRA occurred at 60 and 90min after the administration of the drug in studies I and II, respectively. In study I, a slightly greater reduction of PA levels was found, but there was no significant difference in the magnitude of the reduction between both studies. The present results indicate that food did not exert any significant influence on the clinical effect of captopril.

Cell-mediated immunity (CMI) was evaluated in 26 patients with lipoid nephrosis (LN), 50 patients suffering from chronic diffuse proliferative glomerulonephritis (CGN) without renal sufficiency and 24 healthy controls. The following parameters were measured: delayed hypersensitivity skin test responses to purified protein derivative (PPD) and candida, circulating lymphocytes. T lymphocytes and T lymphocytes with receptors for the Fc portion of IgG (T gamma cells) or IgM (Tmu cells). Patients with LN in relapse had less mean induration of skin reactivity and a smaller proportion reacting to both antigens as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in patients with LN in remission and CGN were similar to those of the control subjects. It was also found that the LN patients in relapse had a significant T lymphocytopenia as well as a significant decrease in absolute numbers of Tmu and T gamma cells, whereas the patients with LN in remission and CGN did not differ significantly from the control population. Thus, the majority of patients with LN in relapse demonstrated an impaired response in a CMI assay system. The disturbed CMI may be secondary to hypoproteinemia and other nutritional factors induced by the nephrotic syndrome.

Spironolactone was administered to spontaneously hypertensive rats (SHRs) in order to examine the urinary excretions of prostaglandin E2 (PGE2) and kinin. Thirteen SHRs were divided into 2 groups: 0.1 ml of sesame oil was administered to one group (the spironolactone-lactone-untreated group, n = 6) and 20 mg of spironolactone in 0.1 ml of sesame oil was administered to the other group (the spironolactone-treated group, n = 7) by the subcutaneous route for 10 days in succession. Determinations were then made of the body weight, blood pressure, urine volume, and excretion levels of Na, K, kinin and PGE2 in the 24-hour urine. After the animals had been killed by decapitation, blood samples were drawn for determination of the plasma renin activity (PRA). The results obtained indicated decreased blood pressure and increased urinary Na excretion in the spironolactone-treated group. On the other hand, the PGE2 excretion level in the 24-hour urine decreased markedly immediately after administration of spironolactone (p

In order to evaluate the relationship between the calcium-calmodulin system and the adenylate cyclase activity of vascular smooth muscle, we examined the effects of several calcium effectors on the basal and stimulated adenylate cyclase activity. Thoracic aortae were removed from Wistar rats and the tissues were homogenated with cold homogenizing buffer containing 1 nM EDTA. Membrane protein fraction of the smooth muscle was prepared by centrifugation at 37,000 g. In this procedure, endogenous guanine nucleotides and contractile proteins remained. The protein fraction was incubated with 2 mM EGTA, 50 microM trifluoperazine, 0.1 microM A23187 or 25 microM calmodulin under basal and stimulated (50 microM isoproterenol, 100 microM GTP and 50 microM forskolin) conditions. The adenylate cyclase activity was determined by a method modified in our laboratory using double isotope counting. Trifluoperazine reduced the basal adenylate cyclase activity significantly (p less than 0.01) as well as the stimulated enzyme activities. A23187 did not affect the basal enzyme activity, but elevated the isoproterenol stimulated enzyme activity significantly (p less than 0.05). EGTA did not affect the basal and stimulated adenylate cyclase activities. Calmodulin elevated the basal enzyme activity significantly (p less than 0.02), but did not affect the stimulated enzyme activities. These results suggest that the calcium-calmodulin system is necessary for maintenance of the adenylate cyclase activity of vascular smooth muscle cells. The calmodulin acting site is considered to be the catalytic subunit, and stimulation of the enzyme is accelerated by calcium ion.

The effects of somatostatin on plasma renin activity (PRA) and blood pressure were evaluated in patients with essential hypertension (EH) and in normotensive subjects. All subjects examined were hospitalized and placed on a diet containing 7-8 g/day sodium chloride and received an intravenous infusion of somatostatin (500 microgram/20 ml of saline, for 60 min) in the basal condition. During somatostatin infusion, the mean blood pressure (MBP) remained unaffected in all patients with EH and the normotensive subjects, while the PRA decreased slightly in the EH group. When the patients with EH were classified according to their renin levels (low, normal and high), parallel significant decreases in MBP and PRA were found only in the high renin group during the somatostatin infusion. No significant change in MBP and PRA was observed in the other groups including the normotensive subjects. To assess the activity of synthetic somatostatin, the plasma levels of growth hormone (GH) and cyclic AMP were measured. These levels were lowered significantly during the infusion and the GH levels showed a rebound 15 min after cessation of the infusion. The cyclic AMP returned to the basal levels, but no rebound was observed. The above data indicate that the fall in blood pressure in the high renin group in the basal condition was probably due in part to reduced renin release by somatostatin, and the maintenance of high blood pressure especially in high renin EH.

Alterations in the concentration of plasma dehydroepiandrosterone sulfate (DHEA-S) and cortisol in patients with essential hypertension (EH) were investigated. The subjects were 25 patients with EH: 7 of low plasma renin activity (PRA) group, 10 of normal PRA group and 8 of high PRA group; 7 normal subjects were used as the controls. Plasma DHEA-S and cortisol were measured before and after the following tests: (1) circadian rhythm (6:00, 16:00 and 24:00), (2) furosemide (0.7 mg/kg) test, (3) ACTH (12.5 IU/4 hr) infusion test, (4) dexamethasone (1.0 mg) test, (5) furosemide (0.7 mg/kg) test under dexamethasone (1.0 mg) treatment, (6) metopirone (1.5 g) test, (7) angiotensin II (8 ng/kg/min, 30 min) infusion test and (8) saline (1000 ml/hr) test. The alterations of the endogenous ACTH-adrenal hormone system as well as the renin-angiotensin-aldosterone system induced by these tests did not cause significant changes of plasma levels of DHEA-S in the 3 groups with EH. However, significant enhancement of plasma DHEA-S was observed after both the administration of exogenous ACTH and angiotensin II. It is considered that the responsiveness of DHEA-S to ACTH may increase in the low and normal PRA groups and that the responsiveness of DHEA-S to angiotensin II may increase in the high PRA group. Based on these results, it is suggested that plasma DHEA-S hardly or only partially participates as a causal factor of EH.

To determine whether patients with systemic lupus erythematosus (SLE) and active nephritis have more profound defects in suppressor cell activity, we studied concanavalin A (Con A)-induced suppressor cell activity (SCA) in 12 patients with lupus nephritis (LN) and 11 patients with chronic mesangial proliferative glomerulonephritis (CGN) without renal insufficiency. The levels of Con A-induced SCA were decreased in patients with LN compared with those in normal controls and those in CGN patients and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, the mean responses of Con A-induced SCA in CGN patients with or without NS did not differ from normal subjects. These findings may lend further insight into the understanding of the immunoregulatory defect in LN.

症例は21才男性.減量を目的に6カ月間に約50kg体重を減少させ,全身倦怠感,意識消失発作を来したため入院となった.入院時,心電図上心拍数36回/分の洞性徐脈を認め,心エコーでは心膜液貯留を認めた.また頭部CTスキャンでは脳萎縮を認めた.血液検査では甲状腺機能検査においてlow T3 syndromeを呈し,さらに経過中, GH値の高値,一過性のGOT, GPT値の上昇等を認めた.本症例は著しい体重減少をきたしているものの,入院時,標準体重を示していることから,我国における神経性食欲不振症の診断基準にあてはまらないが,臨床経過等を総括すると,多彩な臨床症状を呈した神経性食欲不振症の男性例と考えられた.

The influence of a Mg-deficient diet on blood pressure and various hormonal systems was examined in Wistar rats (WR) and spontaneously hypertensive rats (SHR). The WR and SHR were individually divided into 2 groups. The Mg-deficient diet was given to one group, and a Mg-containing diet was given to the other group for 3 weeks. During this experimental period, the body weight, blood pressure, urine volume, blood and urinary electrolytes, plasma steroid hormones, plasma renin activity (PRA), and urinary hormones [kinin, prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and noradrenaline] were examined. Although no significant difference in body weight was observed between the Mg-deficient and Mg-containing diet groups in either the WR or SHR (because the experiments were performed in a pair-fed fashion in both kinds of rat), the blood pressure was increased in the Mg-containing diet group but was unchanged in the Mg-deficient diet group. As regards changes in electrolytes, a decreased urinary excretion of Mg and significantly increased urinary excretion of P were observed in the Mg-deficient diet group in both the WR and SHR. Furthermore, decreased levels of serum Mg and P and increased levels of serum Ca were also noted. In the WR group, the urinary excretion of noradrenaline was significantly increased in the Mg-deficient diet group as compared to the Mg-containing diet group. However, the change was reversed in the SHR group. The plasma steroid hormones and PRA were both significantly low in the Mg-deficient diet group in both the WR and SHR. The urinary excretions of PGE2, 6-keto-PGF1 alpha, and kinin showed no significant differences between the two diet groups. The above results indicate that blood pressure is not affected by the Mg-deficient diet in either the WR or SHR, and the possible participation of the sympathetic nervous system in the mechanism of control of blood pressure may differ somewhat between the WR and SHR. In addition, Mg ion was found to play an important role in the biosynthesis of renin and steroid hormones but to have no such significant role in the urinary excretions of kinin, PGE2, and 6-keto-PGF1 alpha.

The effects of elastase on blood pressure (B.P.) and the urinary excretions of prostaglandins (PGs) and catecholamines in the spontaneously hypertensive rat (SHR) were investigated. Male SHRs (n = 20), castrated at 4 weeks of age, were divided into 2 groups. Elastase was then dissolved in saline (5 mg/ml) and injected subcutaneously (10 mg/kg of body weight) into the SHRs of one of the 2 groups (n = 10) at 5 to 13 weeks of age, and the same dose of saline only was injected subcutaneously into the SHRs of the other group (n = 10) as a control during the same period. B.P. was measured by the tail-cuff method every 2 weeks. Urine sampling and measurement of body weight (B.Wt.) were also performed every 2 weeks. The B.P. in the elastase-administered group (184.1 ± 3.3 mmHg) was found to be significantly lower (p < 0.02) than that of the control group (198.0 ± 4.3) at 9 weeks of age. A significant difference (p < 0.01) in B.P. between the control group (204.0 ± 4.5) and the elastase-administered group (187.3 ± 2.7) was also observed at 13 weeks of age. The urinary excretion of 6-keto-prostaglandin F1α (6-keto-PGF1α) in the control group (5.1 ± 0.4 ng/day/100 g B.Wt.) at 11 weeks of age was significantly lower (p < 0.05) than that of the elastase-administered group (10.4 ± 1.3). The urinary excretions of norepinephrine (NE) and epinephrine (E) in the control group (345.1 ± 39.4 ng/day/100 g B.Wt. (NE), 54.8 ± 8.8 ng/day/100 g B.Wt. (E)) were found to be significantly higher (p < 0.02) than those in the elastase-administered group (216.3 ± 27.7 (NE), and 23.0 ± 3.1 (E)) at 13 weeks of age. The present experiments demonstrated a retardation in the development of hypertension, an increment in the urinary excretion of 6-keto-PGF1α and a decrement in the urinary excretion of catecholamines in the elastase-administered group as compared to the control group. These findings suggest that elastase causes retardation of the development of hypertension in SHRs by some unknown mechanism that increases the excretion of 6-keto-PGF1α and suppresses the excretion of catecholamines.

Deficiency of magnesium with cardiovascular effects is thought to be related to alterations in the biosynthesis of prostaglandins (PGs) in the vasculature. Measurements were made of the PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) outflow from the perfused isolated mesenteric arterial bed and the fatty acid composition of the tissue in rats maintained for 14 weeks on a low magnesium (LMg) diet. The serum Mg levels were significantly decreased and the serum Ca levels were significantly increased in the LMg group as compared to the controls. The arachidonic acid concentration in the triacylglyceride fraction was significantly increased in the LMg group. Long chain polyunsaturates such as 22:4n6 and 22:6n3 were consistently increased in the LMg rats as compared to the controls in both the phospholipid and triglyceride fractions as previously reported in other tissues. The PGE2, 6-keto-PGF1 alpha and TxB2 outflows were significantly increased in the LMg group as compared to the controls. These findings suggest that the biosynthesis of eicosanoids, mainly PGI2, is stimulated in Mg deficiency, and this may provide protection against intracellular Mg depletion and Ca accumulation, so as to counteract to the constricted and hyperreactive state of the vasculature in such a condition.

The pituitary-adrenocortical response to ovine corticotropin-releasing factor (CRF) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) anesthetized with pentobarbital. After intravenous administration of various doses of CRF (0.1, 1.0 and 10 micrograms), the plasma levels of ACTH were significantly increased in both groups. ACTH increments after various doses of CRF were dose-dependent in WKY. ACTH increments after injections of 0.1, 1.0, and 10 micrograms of CRF in SHR were 123.2 +/- 36.5 (SE), 123.0 +/- 52.2 and 60.3 +/- 48.5 pg/ml at 5 min, and 386.3 +/- 73.8, 243.4 +/- 86.6 and 220.0 +/- 31.4 pg/ml at 15 min, respectively. The ACTH increments in SHR at 15 min after administration of 0.1 microgram of CRF were higher (p less than 0.02) than those in WKY. However, ACTH increments in SHR after administration of 10 micrograms of CRF were lower than those in WKY at 5 min (p less than 0.05) and 15 min. These data suggest that the plasma ACTH responses to various doses of CRF represent a dose-unrelated plateau response in SHR. The plasma levels of corticosterone after administration of various doses of CRF did not change significantly and there were no significant differences between the two strains. The results of these experiments suggest that SHR have an abnormal response of the pituitary-adrenocortical axis to CRF, and the abnormal response may be attributable to desensitization of the pituitary to CRF.

The T-colony-forming capacity was examined in 13 normal subjects and 8 patients with biopsy-proven focal glomerular sclerosis (FGS). Fifteen patients with chronic mesangial proliferative glomerulone-phritis (CGN) without renal insufficiency were studied as a disease control. The two main assays used were the counting of T colonies formed by the patients’ lymphocytes, and the measurement of T-colony-forming activity in conditioned medium from cultures of patients’ lymphocytes. The levels of T-colony-forming cells (TCFC) and T-colony-stimulating factor (TCSF) were decreased in patients with FGS compared with those in normal controls and lower in FGS patients with the nephrotic syndrome (NS) than in those without NS. In contrast, these parameters in CGN patients with or without NS did not differ from normal subjects. TCSF activity for TCFC in both normal individuals and FGS patients was removed from media conditioned by phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PHA-LCM) with interleukin-2 (IL-2) receptor bearing cultured T cells. These in vitro findings suggest that IL-2 is the essential factor contained in PHA-LCM. Thus, depressed TCFC in FGS ptients with NS may result in part from impaired generation of TCSF by lymphocytes.

In this study, the effects of angiotensin II (A II, Asn-Arg-Val-Tyr-Val-His-Pro-Phe) and angiotensin III (A III, Arg-Val-Tyr-Ile-His-Pro-Phe) on blood pressure (B.P.), pulse rate, several hormones [plasma renin activity (PRA), plasma aldosterone (PA), ACTH, plasma cortisol (PC), urinary catecholamines and urinary aldosterone] and urinary electrolytes were investigated in 9 male patients with essential hypertension [mean age 36.2 +/- 4.1 (S.E.) years]. A II and A III infusions (8 ng/kg/min, 60 min) were started from 0900 h and blood samples were drawn before, at 15, 30, 45, 60 min after the beginning of the infusions, and at 15 min after their cessation. Urinary samples were collected within 2 hrs before and after the infusions, respectively. A II significantly increased B.P.(p less than 0.01) during the infusions, whereas A III did not increase B.P.. PRA significantly decreased after the infusions of A II and A III (p less than 0.05), but the potency of A II was significantly greater than that of A III (p less than 0.01). PA was increased after both infusions, but in response to A III, a peak was observed at 30 min after the infusion and subsequently, the levels decreased gradually. Significant differences between both responses were found at 45 and 60 min (p less than 0.05) after the infusions. ACTH was unchanged during the infusions, but PC was equipotentially suppressed during the infusions, with the suppression of A II being similar to that of A III. In the responses of urinary catecholamines, noradrenaline and dopamine were equipotentially decreased after the infusions (p less than 0.05). The results of the present study clearly indicate that several differences exist between the biological activities of A II and those of A III. Further systematic experimental studies are needed to resolve the details.

The effects of dibutyryladenosine 3', 5'-monophosphate (DBcAMP), a nucleotide analogue, on blood pressure, serum electrolytes and plasma corticoid concentrations were investigated in 10 normotensive healthy subjects who received a constant diet containing 5-8 g sodium chloride in hospital. The systolic blood pressure did not change after infusion of 0.25 or 0.33 mg/kg/min of DBcAMP for 20 min. On the other hand, the diastolic blood pressure was significantly decreased after the infusion of DBcAMP. The levels of serum sodium and potassium were significantly decreased after the infusion of DBcAMP. After infusion of 0.25 mg/kg/min of DBcAMP for 20 min, the changes in plasma levels of 6 corticoids [progesterone, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC), corticosterone, cortisol and dehydroepiandrosterone sulfate (DHEA-S] revealed no significant changes. After infusion of 0.33 mg/kg/min of DBcAMP for 20 min, the plasma levels of cortisol, corticosterone and 18-OH-DOC were significantly increased and the changes in plasma levels of aldosterone showed a tendency to increase but this was not significant. The plasma levels of DOC and DHEA-S were not appreciably changed, while the plasma levels of progesterone were significantly decreased after the infusion of 0.33 mg/kg/min of DBcAMP. It is speculated therefore that DBcAMP may act to enhance the activity of the sodium-potassium pump and to promote steroid biosynthesis dose-dependently in humans.

Cell-mediated immunity (CMI) was studied in 28 patients with biopsy-proven lipoid nephrosis (LN). The LN patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by impaired delayed hypersensitivity skin reactivity to purified protein derivative (PPD), depressed local graft-versus-host reaction (GVHR), decreased proportion of T lymphocytes and diminished lymphocyte transformation to phytohemagglutinin (PHA). Concanavalin A (Con A)-induced suppressor cell activity (SCA) was found to be significantly increased in LN patients with NS compared to that in normal individuals. In contrast, the mean levels of CMI and SCA studied in LN patients in remission and in patients with chronic mesangial proliferative glomerulonephritis (CGN) did not differ from normal subjects. Our findings support the notion that at least in some LN patients with the NS, activated suppressor cells are present and possibly account for their decreased CMI.

1. Intravenous administration of angiotensin II reduced the adrenaline content, increased the catechol-O-methyltransferase activity, and decreased the monoamine oxidase activity of the rat hypothalamus. 2. Intraventricularly administered angiotensin II reduced the noradrenaline content to a smaller extent. 3. The change produced by intravenous administration of angiotensin might be indirectly caused by a response to angiotensin.

I. Interactions of angiotensin II and norepinephrine in the rat hypothalamus and other brainstem were studied by intraventricular perfusion or/and intravenous administration. (1) Intravenous administration of angiotensin reduced the hypothalamus norepinephrine content. (2) Intraventricularly perfused angiotensin reduced the hypothalamus norepinephrine but did not alter that in other parts of brainstem. Hypothalamus norepinephrine was reduced more by intravenous administration of angiotensin than by intraventricularly perfused angiotensin. II. The involvements of adrenergic mechanism in the central pressor effect of angiotensin II were studied through observation of blood pressure changes following injection of angiotensin II, phentolamine and propranolol into the rabbit lateral ventricle of rabbit brain.(1) Intraventricular administration of phentolamine suppressed the central mediated pressor respons of angiotensin. (2) Simultaneous intraventricular administration of propranolol enhanced the angiotensin pressor effect in anesthetized rabbits.

We investigated the recognition of late potentials in patients with and without organic heart diseases and spontaneous ventricular arrhythmias. None of the normal subjects had late potentials and patients with ventricular arrhythmias but no organic heart diseases, also had no late potentials as well as patients with idiopathic ventricular tachycardias. Late potentials in patients with idiopathic cardiomyopathy were noted more frequently in the dilated type than in the hypertrophic type, especially in those with high grades of ventricular arrhythmias. Patients with old myocardial infarctions had a higher rate of late potentials recognition in cases of sudden death or ventricular tachycardias. On the other hand, we observed lower rates in patients during early stage of acute myocardial infarction in spite of the evidence of a higher rate of ventricular electrical instability. There was no association between ejection fractions, wall motion scores and late potentials. However, a higher recognition of late potentials was found in patients with inferior or posterior myocardial infarction and ventricular aneurysm. We concluded that the late potential must be evaluated in each of the different groups of organic heart diseases in order to estimate the clinical value of ventricular arrhythmias.

The effect of potassium loading on plasma adrenocortical hormones concentrations in 9 patients with essential hypertension (EH) was investigated. The plasma renin activity (PRA), plasma concentrations of growth hormone (GH), ACTH, cortisol, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC) and aldosterone, and serum electrolytes were measured before and after potassium chloride (KC1) infusion (0.33 mEq/kg/h, for one hour). The KC1 infusion caused significant increases in serum potassium levels and plasma levels of GH, ACTH, cortisol, DOC, 18-OH-DOC and aldosterone, while PRA remained unchanged. Regression analysis at 30 min revealed significant positive correlations between delta ACTH and delta cortisol, between delta ACTH and delta DOC, between delta ACTH and delta 18-OH-DOC. However, the relationship between delta ACTH and delta aldosterone was not statistically significant. These results suggest that (1) acute potassium loading causes a significant increase in the plasma ACTH level and increased levels of adrenocortical hormones may be produced by increased ACTH secretion, and (2) it may be considered that a part of the increased level of plasma aldosterone following acute potassium loading may arise from increased ACTH secretion in EH.

Intravenous infusion of somatostatin in mongrel dogs caused a significant decrease in the peripheral plasma renin activity (PRA) enhanced by pentobarbital sodium anesthesia or furosemide treatment. However, the inhibitory activity vanished within 10 min after termination of somatostatin infusion. Intrarenal arterial infusion of somatostatin decreased furosemide-enhanced PRA in renal vein by 24.0%, 16.6% and 8.6% in dose of 0.1, 0.5 and 1.0 microgram, respectively. On the other hand, high doses of the peptide (50-200 microgram) failed to decrease. The changes in PRA occurred in the absence of any alteration in blood pressure during the intravenous infusion under furosemide treatment. In an in vitro study, the addition of somatostatin in doses of 0.01 and 0.05 microgram suppressed the renin release in dog renal cortical cell suspension by 74.3% and 53.6%, respectively. Therefore, in both intrarenal arterial infusion and the cell suspension system, somatostatin was increasingly effective in decreasing renin release towards the lower end of the dose range tested. These results suggest that the effect of somatostatin on hyperreninemia may involve an inhibition of renin release at the cell level in the kidney.

Changes in adrenal renin, which have been regarded as mediator of aldosterone secretion in the adrenal gland, following prolonged ACTH treatment were investigated in male Wistar rats. After 2 days of daily sc injection of ACTH (Cortrosyn-Zinc, 50 micrograms/day), parallel increases in adrenal renin and aldosterone, and plasma aldosterone (PA) were induced. The plasma renin activity (PRA) was slightly but not significantly decreased. Prolonged treatment with ACTH for 8 days increased the adrenal renin, causing a marked reduction in the adrenal aldosterone concentration. The degree of decrease in the PRA was again not significant and similar to that after 2 days of ACTH treatment. Contrary to previout reports which have indicated participation of adrenal renin in the regulation of aldosterone secretion in the adrenal gland, the present results showed reciprocal changes in adrenal renin and aldosterone after prolonged treatment with ACTH. The present findings suggest a complicated relation between adrenal renin and aldosterone secretion in the adrenal gland.

Suppressor cell activity (SCA) was analyzed in 8 patients with focal glomerular sclerosis (FGS) and 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response of normal allogeneic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the FGS patients with nephrotic syndrome (NS) had significantly increased levels of suppression index when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from FGS patients in remission and CGN patients with or without NS, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Thus, the majority of FGS patients with NS demonstrated an alteration in Con A-induced SCA. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

A case report of a 32-year-old male with renovascular hypertension, suspected to be pheochromocytoma as a result of a tentative diagnosis, is given. The suspicion was based on the observation of high levels of urinary noradrenaline on several occasions with the sign of hyperreninemia. Reduction of the urinary noradrenaline levels by the administration of angiotensin converting enzyme inhibitor (SQ-14225) suggested that the high urinary noradrenaline probably resulted from hyperreninemia which reflected high plasma levels of angiotensin II. Radioisotope renography and intravenous urography strongly suggested a reduction of the right renal blood flow, and the final diagnosis of renovascular hypertension was obtained on the basis of renal arteriography. On the other hand, the possibility of a catecholamine releasing tumor was carefully excluded by angiography before undertaking surgical treatment. The affected kidney was transplanted autogenously into the abdominal cavity. The successful operation led to a decrease in plasma renin activity, blood pressure and urinary noradrenaline excretion. In the present case, we were thus unable to define at first whether the primary genesis of hypertension was related to the hyperactivity of the reninangiotensin system caused by renovascular stenosis or a noradrenaline releasing tumor.

In the present study, the pressor activity of 19-hydroxyandrostenedione (19-OH-AD) (which is a kind of androgen) and the presence or absence of the possibility of its role as an amplifier of mineralocorticoid were investigated. 34 Wistar rats of 8 weeks of age were used as the experimental subjects. The rats were divided into 3 groups, the control group (n = 12), 19-OH-AD group (n = 12) and DOCA group (n = 10). The control group was given 0.2 ml of sesame oil, the 19-OH-AD group was given 10 mg of 19-OH-AD dissolved in 0.2 ml of sesame oil, and the DOCA group was given 10 mg of DOCA dissolved in 0.2 ml of sesame oil. This was subcutaneously administered three times a week for 4 weeks, and body weight and blood pressure were observed. At the termination of the experiment, blood was sampled by decapitation, and the serum sodium concentration, erythrocyte sodium content, plasma renin activity (PRA), plasma atrial natriuretic hormone (alpha-rANP), and contents of DOC, corticosterone and aldosterone in adrenal gland were determined. The following results were obtained. The blood pressure at the termination of the experiment was higher than that at the initiation of the experiment by 9.9 +/- 1.9 (S.E.), 31.3 +/- 1.7, and 46.2 +/- 2.0 mmHg in the control, 19-OH-AD and DOCA groups, respectively, where significant elevations were observed in both the 19-OH-AD and DOCA groups as compared with the control group. As to the serum sodium concentration, only the DOCA group showed a significant elevation (p less than 0.001) as compared with the other two groups. However, the erythrocyte sodium contents of both the 19-OH-AD and DOCA groups increased significantly as compared with the control group. Moreover, the increase of the DOCA group was significantly higher (p less than 0.001) than that of the 19-OH-AD, and a significant positive correlation between the elevation of blood pressure and the erythrocyte sodium content was observed (p less than 0.001). As to the PRA value, only the DOCA group showed a significant lowering as compared with the other two groups, whereas alpha-rANP value of the DOCA group showed a significant elevation as compared with the other two groups. As to the contents of steroid hormones in the adrenal gland, all of the steroid hormones were significantly lower in the DOCA group, while those of the 19-OH-AD group were unchanged as were those of the control group.(ABSTRACT TRUNCATED AT 400 WORDS)

In order to investigate the role of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in essential hypertension (EH), the responses of plasma 17-OH-DOC to 7 stimulation tests (furosemide test, adrenal suppression test, angiotensin II infusion test, adrenal stimulation test, metopirone test, saline infusion test and potassium chloride infusion test) and the circadian rhythm were investigated in 18 patients with essential hypertension (low renin group: 8, and normal renin group: 10). From the present study, it micht be thought that plasma 18-OH-DOC does not play an important role in the suppression of PRA in patients with low PRA.

Cell-mediated immunity (CMI) was evaluated in 11 patients with idiopathic membranous nephropathy (MN), 50 patients suffering from chronic proliferative glomerulonephritis (CGN) without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative (PPD), circulating lymphocytes, lymphocyte cell-surface markers (En and EAC rosettes) and functional markers (mitogenic responses to Con A and PHA). The MN patients with nephrotic syndrome (NS) had less mean induration of skin reactivity and a smaller proportion reacting to the PPD antigen as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in MN patients in remission and CGN were similar to those of the control subjects. During the nephrotic stage of MN the proportion of T lymphocytes decreased with simultaneous increase of the proportion of B lymphocytes. It was also found that the MN patients with NS showed impaired lymphocyte reactivity with lower Con A and PHA responses compared to the normal controls. Conversely, the mean mitogenic responses to the antigens in patients with MN in remission and CGN were similar to those of the control subjects. Thus, the majority of MN patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of MN is discussed.

Various doses (5 mg, 12.5 mg and 25 mg) of angiotensin I converting enzyme inhibitor (SQ 14,255, captopril) were administered to 8 patients with essential hypertension on a three-crossover study design, and the time course of mean blood pressure (MBP), plasma renin activity (PRA), plasma angiotensin converting enzyme activity (ACE-A), plasma cortisol (PC) and plasma aldosterone (PA) were determined following administration of the drug. MBP fell in a dose dependent manner, and PRA showed a minor but significant increases in cases receiving 5 and 12.5 mg of the drug. A large and significant increase in PRA was observed following 25 mg of captopril. ACE-A was also reduced in a dose dependent manner. There was no difference between changes in PC at any of the three dose levels. The serum potassium concentration was determined before and 3 hr after 25 mg of captopril treatment and no significant change was observed. In spite of the dose dependent and theoretical changes in the above parameters, lowered responses of PA to each dose of the drug were shown in reverse order against an increasing dose. That is to say, the grade of fall in PA following 25 of captopril was smaller than that following the other doses of the drug, and 5 mg induced a greater decrease in PA than 12.5 mg. Based on these findings, the relatively high dose of captopril in the present study was apparently more effective in increasing some factors which suppressed reduction of PA by a fall in angiotensin II than a low dose of the drug.

Cell-mediated immunity (CMI) was evaluated in 8 patients with focal glomerular sclerosis (FGS), 50 patients suffering from chronic mesangial proliferative glomerulonephritis without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative, circulating lymphocytes, lymphocyte cell-surface markers (neuraminidase-treated sheep erythrocyte and erythrocyte-antibody-complement rosettes) and functional markers (mitogenic responses to concanavalin A and phytohemagglutinin). The FGS patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by decreased responses of the lymphocytes to both concanavalin A and phytohemagglutinin, impaired delayed hypersensitivity to purified protein derivative and a decreased proportion of T lymphocytes as compared with normal subjects. In contrast, the levels of all CMI parameters studied in FGS patients in remission and in patients with chronic glomerulonephritis with or without NS did not differ from normal subjects. Thus, the majority of FGS patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

Cell-mediated immunity (CMI) was evaluated in 76 patients with renal disease by summation of delayed cutaneous hypersensitivity (DHS) responses to 4 test antigens, purified protein derivative (PPD), Candida, mumps and keyhole limpet hemocyanin (KLH). Patients with lipoid nephrosis (LN) in the nephrotic stage had less mean induration of skin reactivity and a smaller proportion reacting to the former 3 antigens as compared with normal controls or LN patients without the nephrotic syndrome (NS). In contrast, the intensity of skin reactivity and the frequency of negative reactions in LN patients in remission and chronic mesangial proliferative glomerulonephritis (CGN) were similar to those of the control subjects. Immune response to KLH was also impaired in LN patients with the NS as measured by skin testing. The data indicate an impaired DHS in LN and suggest that the impairment relates to the clinical stage of disease.

The time courses of mean blood pressure (MBP), plasma renin activity (PRA), plasma aldosterone (PA), serum prostaglandin E (PGE), serum angiotensin I converting enzyme (ACE), and blood levels of angiotensin I converting enzyme inhibitor (SQ 14,225) (captopril) were studied in 6 patients with essential hypertension (5 men and 1 woman, aged 44 +/- 5.6 (mean +/- S.E.) years) before and 30, 60, 120 and 180 min after administration of 25 mg captopril. MBP and ACE began to fall within 30 min and reached a significant minimum between 60 and 180 min after captopril administration. PRA was significantly increased 60 min after captopril administration and continued for 180 min. On the other hand, PA had begun to fall significantly 180 min after captopril administration. The blood levels of captopril were significantly increased 30 min after captopril administration, with a peak at 120 min. The levels at 180 min were half the peak. The levels of PGE were not significantly changed within 180 min after captopril administration. These results suggest a discrepancy between the changes in MBP and the blood levels of captopril. The blood pressure lowering effect may be due to inhibition of angiotensin II (Ang. II) during the short-acting effect, and due to decrease of PA, metabolites of captopril, increase of kinin in the blood, inhibition of the slow pressor effect of Ang. II, increases of other depressor hormones such as prostacyclin and other depressor mechanisms during the long-acting effect.

Suppressor cell activity (SCA) was analyzed in 8 patients with idiopathic membranous nephropathy (MN) and in 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response of normal allogenic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the MN patients with nephrotic syndrome (NS) had significantly increased levels of suppression index (SI) when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from MN patients in remission and CGN patients with or without NS, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Thus, the majority of MN patients with NS demonstrated an alteration in Con-A-induced SCA. The possible significance of these phenomena in the pathophysiology of MN is discussed.

We evaluated long-term combined vasodilator therapy (hydralazine or ecarazine + isosorbide dinitrate) in 29 patients with chronic congestive heart failure resistant to the optimal conventional therapy. There were 24 men and 5 women, aged 28 to 76 years (mean 52 y/o). The etiology of heart failure was congestive cardiomyopathy in 24 patients, ischemic cardiomyopathy in 4 patients and advanced mitral regurgitation due to calcified mitral annulus in 1 patient. There were 21 patients in NYHA class III and 8 patients in NYHA class IV. All patients continued their previous therapeutic regimen during the period of this study. Hemodynamic measurements were performed with a triple lumen flow-directed balloon-tipped catheter in 20 patients to evaluate the effects of vasodilator therapy. In the rest of 9 patients, heart rate, blood pressure, chest X-ray examination for heart size (CTR) and M-mode echocardiograms for ejection fraction (EF) were monitored. The hemodynamic responses to the combined vasodilator therapy in 20 patients showed significant decreases in afterload and preload concomitant with an increase in cardiac output. The noninvasive evaluation of combined vasodilator therapy in 9 patients resulted in significant improvement in CTR and EF. We also noted a significant improvement in their symptoms of 29 patients. Side effects and drug toxicity were uncommon during vasodilator therapy. It is concluded that the combined vasodilator therapy is most useful adjunctive therapy in the management of severe refractory heart failure. Moreover, long-term nonparenteral vasodilators can be administered even at outpatient clinic without hemodynamic monitoring.