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Biomedical subjects

R Yabe

Publications and source records attributed to R Yabe.

31 records · Page 2Linked to original sources

Active and inactive renin-like enzymes in the brain of spontaneously hypertensive rat.

Renin-like enzyme(s) in the brain of spontaneously hypertensive rat (SHR) were activated unequivocally by trypsin. The highest concentration of the active renin-like enzyme was localized in the hypothalamus (1.03 +/- 0.25 ng angiotensin I/mg of protein per h, mean +/- S.D.), followed by the striatum (0.51 +/- 0.21), thalamus (0.40 +/- 0.08), midbrain (0.33 +/- 0.04), medulla oblongata (0.25 +/- 0.01), cerebral cortex (0.21 +/- 0.03), and cerebellum (0.14 +/- 0.03), while the highest concentration of the inactive renin-like enzyme was localized in the hypothalamus (0.86 +/- 0.17), followed by the striatum (0.47 +/- 0.15), thalamus (0.32 +/- 0.09), cerebellum (0.29 +/- 0.04), midbrain (0.26 +/- 0.02), cerebral cortex (0.24 +/- 0.04), and medulla oblongata (0.10 +/- 0.03). The active renin-like activity in the thalamus of SHR was significantly lower than that of age- and sex-matched normotensive Wistar-Kyoto (WKY) rats. Furthermore, the inactive renin-like activity in the striatum, thalamus, cerebellum, midbrain, and medulla oblongata of SHR was significantly lower than that in the corresponding areas of WKY rats. Although the precise mechanisms underlying the conversion of inactive to active renin-like enzyme in the brain remain to be resolved, these results may offer a new aspect for the role of the brain renin-angiotensin system in the initiation and/or development of hypertension of SHR.

Animals↗

Biochemical characterization of angiotensin-converting enzyme in human neuroblastoma tissue.

High activity of angiotensin-converting enzyme was demonstrated in human neuroblastoma tissue. This activity required the presence of chloride ion and was almost completely inhibited by a specific converting enzyme inhibitor captopril (10 nM), indicating that the activity measured is indeed angiotensin-converting enzyme. Furthermore, the biochemical features of the enzyme were closely similar to the well-known properties of human lung converting enzyme, such as molecular weight (290,000), optimum pH (8.0-8.5), the presence of glycoprotein residues, and dependence on chloride ion concentration. These results provide definitive evidence for the presence of true angiotensin-converting enzyme in human neuroblastoma tissue.

Angiotensin-Converting Enzyme Inhibitors↗

A hitherto unreported case of 21-hydroxylase deficiency associated with Bartter's syndrome and a balanced 6-9 translocation.

A description is given of a girl with the non-salt-losing type of congenital adrenal hyperplasia (CAH) and with Bartter's syndrome. In addition, the patient had a balanced translocation between 6q and 9p. Although the possibility cannot be ruled out fully that an excess of progesterone might modify the renin-aldosterone axis to some extent, the finding that dexamethasone therapy improved the clinical features of CAH but failed to correct metabolic disorders in electrolyte balance strongly suggests the coexistence of the two clinical entities. Chloride transport at the distal tubule was impaired moderately in the patient, which suggests that her defective reabsorption of chloride was responsible for the impaired renal handling of sodium that is often observed in patients with Bartter's syndrome. It appears that the reciprocal translocation is unrelated to both CAH and Bartter's syndrome since the same translocation was found in her healthy mother and siblings.

Adolescent↗

Treatment of pheochromocytoma with dilevalol.

Dilevalol, an alpha- and beta-blocking agent, has been evaluated in two patients with pheochromocytoma. Dilevalol could be a useful agent for the treatment of pheochromocytoma, especially for the adrenaline-dominant type.

Administration, Oral↗

Biochemical evidence for existence of immunoreactive renin in human prolactinoma tissue.

High activity of renin was demonstrated in human prolactinoma tissue. This activity was almost completely inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 5.04 ng of angiotensin I generated/mg of protein per h, comparable to that of the pituitary tissue prepared from postmortem human subjects. The biochemical properties of the prolactinoma renin were generally similar to those of well-known kidney enzyme, such as molecular mass (Mr = 46,000), optimum pH (6.0), and glycoprotein nature. However, the isoelectric points (pI) of the prolactinoma renin (pI = 4.90, 5.04, 5.24 and 5.41) differed somewhat from those of plasma and kidney renins reported hitherto. These results indicate that true renin can be produced in human prolactinoma tissue.

Chromatography, Affinity↗

[A case of 21-hydroxylase deficiency and Bartter's syndrome associated with a balanced 6-9 translocation].

A 17-year-old female weighing 37 kg and 140 cm in height was referred to our hospital for evaluation of dwarfism and primary amenorrhea. She was delivered with 3350 g in weight and 50 cm in height after a ten month pregnancy without complications. No abnormal findings were revealed in physical appearance except critomegaly. Episodes of nausea, vomiting and dehydration were rare throughout her childhood, but she had a tendency to salt craving. At the age of 14, her height was 140 cm. On admission, her physical development was markedly retarded for her age, except external genitalia. Diffuse pigmentations on the trunk and extremities were observed. Her blood pressure was normal (112/62 mm Hg). Serum potassium concentration was 2.9 mEq/L. Arterial-blood gas analysis revealed metabolic alkalosis. Both of renin activity (PRA) and aldosterone concentration (PAC) in plasma at rest were markedly elevated to 15.5 ng/ml/h and 107.1 ng/dl, respectively. The plasma concentrations of pregnenolone (1449 ng/dl), progesterone (178 ng/dl), 17-OH-pregnenolone (1613 ng/dl), 17-OH-progesterone (180 ng/dl), dehydroepiandrosterone (3706 ng/dl), androstendione (824.6 ng/dl) and testosterone (900 ng/dl) were high, whereas deoxycorticosterone (15.7 ng/dl), corticosterone (0.65 microgram/dl) and cortisol (6.8 micrograms/dl) were within normal limits. Urinary 17-KS excretion showed high levels between 65.7 and 109.4 mg/day, while urinary 17-OHCS excretion was normal (5.7-7.0 mg/day). Vascular response to angiotensin II (A-II) was attenuated. Distal fractional chloride reabsorption was decreased (CH2O/CH2O+CCl = 0.62, normal: 0.92 +/- 0.04). Moderate hyperplasia of the juxtaglomerular cells was demonstrated in biopsy specimen of the kidney. Cytogenetic studies showed a 46, XX chromosome constitution with translocation of the long arm of chromosome 6 to the short arm of chromosome 9. Her mother as well as younger brother and sister, whose electrolytes and arterial-blood gas analysis showed normal values, had chromosomes with the same translocation. Treatment with dexamethasone (2 mg/day) reduced every adrenal steroids to normal range, but PRA and PAC remained high levels. Furthermore, neither hypokalemic alkalosis nor vasoreactivity to exogenous A-II was improved. Indomethacin (75 mg/day) decreased urinary excretion of prostaglandin E2 from a high level of 738.4 ng/day to 433.4 ng/day and normalized metabolic alkalosis. Vascular response to A-II was moderately improved. However, serum potassium remained low.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Demonstration and characterization of angiotensin-converting enzyme in human pituitary tissue.

High activity of angiotensin-converting enzyme was demonstrated in human pituitary tissue. This activity required the presence of chloride ion and was almost completely inhibited by a specific converting enzyme inhibitor captopril (10 nM), indicating that the activity measured is indeed angiotensin-converting enzyme. The specific activity of the enzyme was 1.68 +/- 1.20 nmol hippuric acid generated mg of protein-1 min-1 (mean +/- SD, for 11 specimens). The biochemical features of the enzyme were closely related to the well-characterized human lung converting enzyme, such as molecular weight (290,000), optimum pH (8.0-8.5), the presence of glycoprotein residues, and dependence on chloride ion concentration. These results provide definitive evidence for the presence of angiotensin-converting enzyme in human pituitary tissue.

Chlorides↗

Antihypertensive effect of a new calcium channel blocker, FK 235, in essential hypertension.

The antihypertensive effect of a new calcium channel blocker (FK 235) were evaluated in 10 patients with mild-to-moderate essential hypertension. The study consisted of 4 weeks of placebo and 12 weeks of the drug, 2 to 4 mg twice a day. Overall systolic and diastolic blood pressures (mean +/- SE) were reduced from 173 +/- 4 to 158 +/- 2 mm Hg (p less than 0.001) and from 97 +/- 2 to 89 +/- 1 mm Hg (p less than 0.001), respectively, with a dose of 5.6 +/- 0.7 mg/day. No relevant changes in heart rate, body weight, and plasma levels of renin activity and aldosterone concentration were observed. No side effects were encountered during the therapy. Our data indicate that the novel active calcium channel blocker can be used as a safe, effective and well tolerated antihypertensive for the treatment of essential hypertension.

Adult↗

[Evidence for the existence of inactive renin in the rat brain. Part II. Distribution of inactive renin in the brain of spontaneously hypertensive rats].

Inactive renin in the brain of spontaneously hypertensive rat was investigated. The results are as follows. Treatment with either trypsin or glandular kallikrein of the brain tissue extract caused a rapid and apparent increase in the renin activity at either 0 or 27 degrees C. The molecular weight of the active renin was estimated to be 41,000 or 50,000 daltons, while that of the trypsin-activatable inactive renin was found to be 44,000 or 57,000 daltons on a column chromatography with Sephadex G-100. The contents of the active renin was the highest in the hypothalamus, followed by the striatum, thalamus, midbrain, medulla oblongata, cerebral cortex and cerebellum, while the contents of the trypsin-activatable inactive renin was the highest in the hypothalamus, followed by the striatum, thalamus, cerebellum, midbrain, cerebral cortex and medulla oblongata. These results suggest that inactive renin(s) exist in the brain of spontaneously hypertensive rat. It seems likely that the brain renin-angiotensin system is modulated by the conversion of inactive to active renin(s), which, in turn, plays at least in part a role in the blood pressure regulation through generation of angiotensin II in spontaneously hypertensive rats.

Animals↗

Acute effects of the new oral angiotensin converting enzyme inhibitor 1-(D-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine (Alacepril) in essential hypertension.

In 15 patients with mild-to-moderate essential hypertension a new orally active angiotensin converting enzyme inhibitor, 1-(D-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine (Alacepril), was administered with a single oral dose of 50 mg to evaluate its antihypertensive effect. Following Alacepril plasma angiotensin converting enzyme (ACE) activity was inhibited by approximately 75% within 2 h. Plasma renin activity increased slightly whereas plasma levels of aldosterone decreased significantly. Blood pressure fell markedly not only in patients with high renin levels but also in those with low renin levels. Nevertheless, the magnitude of blood pressure reduction was correlated with the pre-treatment plasma renin values (r = -0.602, p less than 0.05 systolic, r = -0.667, p less than 0.01 diastolic). No relevant changes in pulse rate was observed. These findings demonstrate that in essential hypertension the novel orally active ACE inhibitor Alacepril exerts marked antihypertensive effect, which may offer a new effective approach to treatment of hypertension.

Administration, Oral↗