Search

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.

Interleukin-1 (IL-1) is a pleiotropic factor, eliciting a broad set of immunologic and inflammatory events. We have previously shown that IL-1 is present in inflamed glomeruli. To evaluate factors that might regulate of IL-1 production, we tested the effects of substances accessible to mesangial cells (MC): immune complexes (IC) are known to modulate MC function. We have attempted to assess the ability of soluble IC derived from rat glomerular basement membrane to induce the production of IL-1. When isolated MC were incubated with the soluble IC, substantial amount of IL-1 could be detected in the supernatants as measured by the mouse thymocyte assay. To block the effect of prostaglandins on the IL-1 assay, we cultured the MC with the addition of indomethacin and assayed IL-1 activity in the culture supernatants. The use of indomethacin resulted in a further increase in IL-1 production. These biological activities were neutralized by a specific antibody to IL-1. In the present report, we show that IC represent important sources of stimulation of MC for the production of IL-1. We speculate that IC could augment local inflammatory responses in the kidney partly due to their capacity to induce the production of IL-1.

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)

Serum from patients with membranoproliferative glomerulonephritis (MPGN) and acute poststreptococcal glomerulonephritis (APSGN) accelerated the decay of the cell bound C4b2a (C42) and C4b hemolytic activity relative to pooled normal human serum (pNHS) after 5 min incubation at 30 degrees C in EDTA-GVB. The accelerated decay of the C42 hemolytic activity was heat stable (56 degrees C 30 min) and was inhibited by monoclonal antibody against human C4 binding protein (MoAb:C4BP) or C4 binding protein (C4BP) depleted serum. C4 nephritic factor (C4NeF) was employed to stabilize the labile classical pathway C3 convertase C42 complex. Serum from patients with MPGN and APSGN reduced the C4NeF stabilizing activity. Sera from 32 of 46 patients with MPGN and all of 7 patients with APSGN reduced the C42 hemolytic activity relative to 50 normal human serum (NHS) after 5 min incubation at 30 degrees C in EDTA-GVB, and there was no relationship with the serum concentration of C4BP. In vivo, accelerated decay of C42 convertase might interfere with the clearing and processing mechanism of circulating immune complexes (IC) by reducing deposition of C3b on the IC lattice.

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.

The IgG fraction of serum from patients with membranoproliferative glomerulonephritis (MPGN) types I and II or partial lipodystrophy (PLD) was found to contain C3 nephritic factor (C3NeF) which reacts with the alternative pathway C3 convertase C3bBb and stabilizes it. Two types of C3NeF were detected, of which one was heat sensitive (56 degrees C for 30 min) and properdin dependent (C3NeF:P) but the other was heat stable and properdin independent (C3NeF:nP). C3NeF:P was found in sera from patients with MPGN types I and II and it displayed the properties of properdin and IgG. C3NeF:P was observed in patients with reduced serum concentrations of C3 and terminal complement components (TCC), and the generation of SC5b-9 complex was increased in mixtures with normal human serum. C3NeF:nP was found in sera from patients with MPGN type II and PLD, whose sera revealed a selective decrease in C3 concentrations.

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.

Plasma renin activity (PRA) was measured in 14 control subjects and 27 patients with essential hypertension (EH) (low renin group: 9, normal renin group: 11, and high renin group: 7) before and after the following stimulation tests. Test procedures: 1) Circadian rhythm (0600, 1600 and 2400h). 2) Adrenal stimulation test (ACTH: 12.5 I.U.). 3) Adrenal suppression test (Dexamethasone: 1.0 mg). 4) Metopirone test (1.5 g). 5) Angiotensin II infusion test (8 ng/kg/min). 6) Saline infusion test (1000 ml/hr). Patients with low PRA showed significantly lower levels of PRA than those of other two groups in circadian rhythm, after 2 hours of ACTH infusion and after angiotensin II infusion. Furthermore, these patients showed significantly higher responses of PRA than other two groups after furosemide test under dexamethasone and after metopirone test. In case of saline infusion test, patients with low and normal PRA did not show significantly decreased levels of PRA after the infusion, though all patients with high PRA and all control subjects showed significantly decreased levels of PRA. From the present studies, it might be concluded that patients with low PRA has an unknown mineralocorticoid excess which is ACTH dependent and 11 hydroxylated and some of hypertensive patients have an abnormality in their renin-angiotensin-aldosterone volume feed back loop as a factor for hypertension.

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.

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, and 0.1 ml of sesame oil was administered to one of 2 groups (spironolactone-untreated group) (n = 6) and 20 mg of spironolactone in 0.1 ml of sesame oil was administered to the other group (spironolactone-treated group) (n = 7) by the subcutaneous route for 10 days in succession, followed by the determination of body weight, blood pressure, urine volume, excretion levels of Na, K, kinin and PGE2 in 24-hour urine. Blood samples were drawn after these animals were killed by decapitation for determining plasma renin activity (PRA). In consequence, decreased blood pressure and increased urinary Na excretion were observed in the spironolactone-treated group. On the other hand, PGE2 excretion level in 24-hour urine markedly decreased immediately after administration of spironolactone (p less than 0.05) and was maintained at lower levels up to the end of experiment. However, 24-hour urinary kinin levels showed similar changes in the spironolactone-treated group and the untreated group with no significant difference between the two groups. These results indicate that spironolactone has a suppressive effect on urinary PGE2 excretion, the activity of which is not mediated by kinin production in the kidneys but produced by a direct action of spironolactone itself.

In order to systematically analyze the regulation and metabolism of steroid hormones in a case of primary aldosteronism with multiple lesions, including adenoma and nodular hyperplasia of the left adrenal gland, the amounts of 9 steroids (progesterone (P), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH-B), aldosterone (Aldo), 17 alpha-hydroxyprogesterone (17-OH-P), 11-deoxycortisol (S), cortisol (F) and dehydroepiandrosterone sulfate (DHEAS)) contained in the plasma and in the adrenal tissues were measured. The patient (a 39-year-old female) was admitted to our hospital because of hypokalemia and hypertension. A diagnosis of primary aldosteronism was made on the basis of a complete evaluation, and an adenoma (1.8 x 1.2 cm), a nodular hyperplasia (0.5 x 0.5 cm), a microadenoma and a cortical nodule were found on the left adrenal gland. In vivo studies revealed that the plasma level of Aldo was high, but those of the other steroid hormones were within the normal range. After ACTH infusion, the plasma levels of the 9 steroid hormones increased by 2 to 17 times the base levels. In particular, the responses of DOC and B were markedly high. In vitro studies on P, DOC, B, Aldo and F content in the adenoma (A), the nodular hyperplasia (A'), the adjacent adrenal tissue (C) and the right normal adrenal tissue (D) revealed that, except for F, they were highest in A, followed by A', D and C in that order. In incubation studies with ACTH using A and C, it was found that the levels of 8 steroid hormones with the exception of DHEAS were high in A than in C. In particular, the response of B in A was markedly increased. These findings suggest that aldosteronoma produces 8 steroid hormones under conditions of excess ACTH, while at physiological levels of ACTH, it produces only Aldo in excess.

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.

In order to evaluate the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-AD), which has been reported to be an amplifier of mineralocorticoid, the changes in several humoral factors were observed in 19-OH-AD treated rats as compared to those in DOCA hypertensive rats. Twenty-five male Wistar rats were castrated at 11 weeks of age, and the experiments were begun at 12 weeks of age. The rats were divided into 3 groups. The control group (n = 8) was given an s.c. injection of 0.2 ml of sesame oil. The 19-OH-AD group (n = 10) was injected s.c. with 10 mg of 19-OH-AD dissolved in 0.2 ml of sesame oil, and the DOCA group (n = 8) was injected s.c. with 10 mg of DOCA dissolved in 0.2 ml of sesame oil three time weekly. The urine was collected for a period of 24 hours, and the urine volume, and urinary excretions of electrolytes, prostaglandin E2 (PGE2), kinin and catecholamine were measured before and after the start of the experiment. The systolic blood pressure (S.B.P.) was measured by the tail-cuff method. The S.B.P. values before and at 9 weeks after the start of the experiments were 136.7 +/- 3.8 and 156.0 +/- 2.6 mmHg in the 19-OH-AD group, and 140.6 +/- 5.6 and 179.3 +/- 5.5 mmHg in the DOCA group, respectively. Body weight, which was elevated in both groups, was higher in the 19-OH-AD group than in the DOCA group. Water intake and urine volume were significantly (p less than 0.001) increased only in the DOCA group. The urinary Na/K ratio was significantly (p less than 0.001) elevated in the DOCA group as compared to that in the other two groups. However, there was no significant difference in urinary Na/K ratio between the control and 19-OH-AD groups. The urinary PGE2 and kinin excretions were significantly (p less than 0.01) increased in the DOCA group but did not change appreciably in the 19-OH-AD group. The urinary catecholamine excretion was significantly increased in the DOCA group. However, there were no differences in the catecholamine excretion between the control and 19-OH-AD groups.(ABSTRACT TRUNCATED AT 400 WORDS)

The locus coeruleus was subjected to biphasic electrical stimulation, and a group of deoxycorticosterone acetate (DOCA)-salt hypertensive rats revealed a greater pressor response than a group of normotensive control rats. The pressor threshold current (i.e. minimum current to raise the arterial pressure by 10 mm Hg) of DOCA-salt hypertensive rats was also lower. The threshold current was low even in the prehypertensive stage of DOCA-salt treated rats. During arterial pressure fall, the pressurethreshold current lowered only in normotensive rats and neither group underwent a change during pressure rise. These data indicated that the locus coeruleus had a pressor role and it had been accelerated in DOCA-salt treated rats before hypertension was evident. Following bilateral electrical lesions of the locus coeruleus no significant differences were observed in the arterial pressure changes, while vascular reactivity to norepinephrine did not differ between the two groups. The results suggest that the locus coeruleus may be involved in the development of hypertension but may not be important in the maintenance of it.

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.

A simplified screening test for differentiating primary aldosteronism (PA) from low renin essential hypertension (LREH) is presented. Nine patients with LREH and 5 patients with PA due to adrenal adenoma were studied. In the patients with LREH, the levels of plasma renin activity (PRA) before and after treatment with furosemide (0.7 mg/kg, i.v.) and a 2-hour ambulation under treatment with dexamethasone (1.0 mg) (dexamethasone + furosemide test) increased briskly, compared to the levels of PRA before and after treatment with furosemide (0.7 mg/kg, i.v.) and a 2-hour ambulation (furosemide test). In patients with PA, there was no significant difference between the mean levels before the furosemide test and before the dexamethasone + furosemide test, or between the mean levels after the furosemide test and after the dexamethasone + furosemide test. These results suggest that the suppression of PRA in patients with LREH may be related to a factor controlled by dexamethasone. It is concluded that the dexamethasone + furosemide test is useful for differentiating PA due to adenoma from LREH.

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.

Fibrinopeptide A (FPA) is a peptide released from N-terminal ends of Aα chain of fibrinogen molecule in initial stage of fibrinogen-fibrin conversion. It is, therefore, considered that the determination of FPA in blood or urine is able to be a direct proof of fibrin formation occuring in vivo.The authors studied the radioimmunoassay of FPA of blood and urine in normal adults as well as in patients with renal diseases. In determination of FPA, FPA-antiserum, standard FPA and tyrosyl-FPA obtained from IMCO. Co. Ltd. (Sweden) were used. Procedure of FPA assay was accorded with the method developed by Nossel, et al.. The authors ascertained by preliminary experiment that the Nossel's method could be applied to urinary FPA determination. Our results indicated that, 1) FPA values in clotting reflected strongly to thrombin action. A certain level of FPA-immunoreactivity of fibrinogen split products by plasmin (FgDP) was recognized. In purified in-vitro system, FPA-immunoreactivity of FgDP was 20% when compared to the fibrin clotting system of 100%. While, almost negative (0.3%) immunoreactivity was observed in fibrin split products by plasmin (FDP). 2) Mean and range of blood FPA values of 30 normal adults was 0.3±0.4ng/ml, and this was well closed to the values reported by Nossel, et al.. 3) Urinary FPA values of 33 normal adults were 0.8±0.7ng/ml. It was noted that the urinary FPA of patients with renal deseases showed higher values in many cases in contrast to the normal urine.

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.

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.