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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.

CAPD歴約6か月の51歳, 男性が, 突然, 除水量低下と体重増加が出現し, 胸部X線検査で右側胸水貯留が認められたため, 精査加療目的で入院となった. 末梢の浮腫および炎症所見は認められず, 胸水中糖濃度が血糖より高かったため, 腹膜灌流液の胸腔への移行を疑い, 99mTc-MAAを用いて確定診断を施行した, 本症の治療として, 胸水排出後に自家血の胸腔内注入による胸膜癒着術を試みたところ, 単独では無効であったが, CAPDの短期間中断およびその後に1回注液量を減少させたCAPDを併用することによって効果が得られた. 本療法は, 副作用なしに施行できたが, 永久的な胸膜の癒着が得られるかどうかは不明であり, 今後長期的に経過を観察する必要がある.

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.

Plasma exchange has been employed in many fields. We reviewed its effect in 5 cases of refractory hyperbilirubinemia after acute liver dysfunction excluding fulminant hepatitis. Three liters of plasma replacement per session of plasma exchange was sufficient to remove bilirubin from the plasma effectively, but plasma exchange over a period of 3 consecutive days was needed to remove bilirubin from the whole body. In cases of a serum total bilirubin concentration of above 30mg/dl, the effect was less and far more plasma exchange was required. Posttransfusional hepatitis occurred in a few cases. Although plasma exchange certainly represents the most effective method for reducing the bilirubin levels, further studies on the effects of plasmaperfusion are needed since with this procedure post-transfusional hepatitis never occurs.

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)

The effect of intraperitoneal administration of heparin to patients on continuous ambulatory peritoneal dialysis (CAPD) remains obscure. We examined 8 patients on CAPD to investigate its effect. When 2.5 U/ml or 5 U/ml of heparin was given intraperitoneally, t1/2 of heparin activity in the dialysate was 0.5 to 2 hrs, and 6 hrs after administration its activity was 0.5 U/ml and 1.4 U/ml respectively. Whole blood clotting time was hardly affected because the transfer of heparin to the plasma was minimal. The plasma antithrombin III (AT -III) levels were comparable to patients on hemodialysis, but the AT-111level in the dialysate was only 1.5% of those in the plasma. We conclude that the intraperitoneal administration of heparin at these doses is effective in preventing fibrin precipitation when intraperitoneal AT -III levels are expected to be relatively increased such as at the start of CAPD or in the presence of peritonitis.

昭和58年から昭和63年までの当院におけるCAPD社会復帰患者31名 (男性22名, 女性9名, 平均年齢47歳) を対象とし, 平成2年3月の時点での患者の転帰・予後をretrospectiveに検討した. HDに移行した症例10名 (32%), 腎移植を受けた症例2名 (6%), 死亡4名 (13%) であり, CAPDを継続している症例は15名 (48%) であった. HDに移行した原因のうち, 頻回の腹膜炎により社会復帰が困難であった症例が5名と最も多く, またHDに移行した症例のうち80%が, 腹膜炎を合併しなければCAPDをさらに継続できた可能性があった. 以上のことにより, 腹膜炎の予防により, CAPDの長期継続は可能と思われ, そのためには適切な患者選択および患者教育が重要である.

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.

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.

A sudden coronary thrombus formation was documented by chance during cardiac catheterization in a patient with postinfarction angina. The thrombus was successfully treated with intravenous urokinase and heparin infusions, and there after, coronary angioplasty was performed without any complication.

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 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.

It is known that membranoproliferative glomerulonephritis (MPGN), hypocomplementaemia and C3 nephritic factor (C3NeF) are closely related to each other, and the presence or absence of C3NeF in the serum is important for evaluating the nature of MPGN. However, some difficulties have been encountered in detecting this factor and therefore a new assay permitting the direct detection of C3NeF without purifying IgG from the patient's serum has been devised. Using this assay method, C3bBb-stabilizing activity was observed even in sera from MPGN patients who were non-hypocomplementaemic. Furthermore, among 98 cases with hypocomplementaemia. C3NeF was found to be absent in 66 cases.

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.

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.