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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.

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.

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)

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.

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.

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.

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 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.

Although mucolipidosis, a fatal metabolic storage disorder, is associated with cardiovascular abnormalities, detailed, non-invasive cardiac examinations have not been well documented. We studied 4 children with type II and type III mucolipidosis, 3 of whom had unequivocal evidence of aortic regurgitation characterized by phonocardiography and M-mode echocardiography. Two-dimensional echocardiography showed an aortic valve prolapse in 3, a mitral valve prolapse in 2 and a tricuspid valve prolapse in 1. The QT interval was prolonged in 2 cases. In 1 autopsy case, we found considerably thickened and retracted aortic, mitral, and tricuspid valves, and accumulation of the foam cells in the myocardium. Echocardiography revealed similar findings in another 3 cases. We conclude that cardiac manifestations in this disorder should be examined carefully particularly by the use of echocardiography which is an excellent technique for detecting cardiovascular abnormalities in mucolipidosis.

When the ventricle is electrically stimulated at a faster rate, the cessation of the drive is followed by a temporary suppression of automaticity (overdrive suppression). The effects of lidocaine and verapamil on overdrive suppression were studied in dogs. Lidocaine slowed the ventricular escape rate and prolonged the pause following overdrive; occasionally, it was about twice the next succeeding RR interval. On the contrary, verapamil influenced neither the ventricular escape rate nor the pause following overdrive. It is suggested that lidocaine not only suppresses the automaticity of ventricular escape pacemaker but also induces exit block and that the spontaneous depolarization of the ventricular pacemaker is not slow channel-dependent.

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.

Fibrinopeptide A (FPA) in both urine and plasma was measured using radioimmunoassy in order to confirm the presence of intrarenal coagulation in renal disease. Patients were divided into 2 groups according to the urinary FDP (mg)/urinary protein (g) ratio: Group A, patients with above 1.0 of the ratio. Group B, patients with less 0.5 of the ratio.The results were as follows: (1) Urinary FPA did not correlate to plasma FPA. (2) Urinary FPA were significantly high in group A, but were normal in group B. (3) The renal functions of group A were all markedly deteriorated. But, the renal functions of group B showed widely spread values. (4) Heparin administration on group A patients reduced their urinary FPA with improvement of renal functions and azotemia.These results indicate: (1) Above 1.0 of urinary FDP (mg)/urinary protein (g) ratio and high urinary FPA reflect the presence of extensive intrarenal coagulation. (2) Extensive intrarenal coagulation was occured only in the patients with markedly deteriorated renal functions. (3) These patients were only a few in renal disease patients. (4) It might be difficult to get good clinical improvement in chronic patients even when intrarenal coagulation is both accuratetly detected and completely eliminated by anticoagulants. (5) However, anticoagulant therapy has proved to be benificial in acute pacients with extensive intrarenal coagulation.

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.

To clarify the vasoconstrictory action of leukotriene D4 (LTD4) on the injured coronary arteries, 8 mongrel dogs were denuded by basket balloon catheter (denuded group) and LTD4 (0.33μg) was directly administered into left anterior descending coronary artery. Hemodynamic parameters as well as epicardial ECG were recorded after LTD4 administration. Another 8 non-denuded dogs were served as control.Furthermore, the influence of denudation to LTD4-induced coronary spasm was determined by coronary arteriography (CAG) . In results, a significant reduction of coronary blood flow (from 1.03±0.13 to 0.49±0.05 ml/kg/min. P

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.