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S Niimura

Publications and source records attributed to S Niimura.

At least 37 records · Page 2Linked to original sources
PubMed1991

[A case of idiopathic hypoparathyroidism complicated with chronic thyroiditis].

It has been suggested that autoimmunity and genetic factors may play a specific role in the development of idiopathic hypoparathyroidism. We reported a case of idiopathic hypoparathyroidism complicated with chronic thyroiditis. The patient, a woman 40 years old, visited our clinic because of tetany of both hands and dizziness. She was of short stature with a round face. She also had a goiter, hypocalcemia, hyperphosphatemia and decreased parathyroidal function, but renal function was normal. Her TSH level was slightly high with a positive microsome test (x 1600), and the levels of thyroid hormones tended to be low. Based on Ellsworth-Howard test findings, a diagnosis of idiopathic hypoparathyroidism was made, with the complication of chronic thyroiditis confirmed by the thyroidal biopsy. Administration of l alpha-OH-D3 normalized the level of serum calcium. No special treatment was given for the chronic thyroiditis in order to observe its natural course. Her TSH returned to normal, and the level of thyroid hormones was increased to normal ranges. Tests were positive for anti-adrenal antibody and anti-gastric antibody. The complication of chronic thyroiditis, an autoimmune disease, and a positive finding for every antibody suggested the possible involvement of autoimmunity in the mechanism of development of idiopathic hypoparathyroidism. The administration of 1 alpha-OH-D3 resulted in an increase in the serum calcium level and also normalization of levels of TSH and thyroid hormones. Thus, it is likely that the elevation of the calcium ion or immunoregulation by active vitamin D may have induced the increase in thyroid hormone secretion.

Adult↗
PubMed1991

The antihypertensive mechanism of delapril, a newly developed converting enzyme inhibitor, is related to the suppression of vascular angiotensin II release in the spontaneously hypertensive rat.

Accumulating evidence suggests an important role of vascular renin-angiotensin system (RAS) in the local control of arterial tone. To further gain insight into the significance of vascular RAS in hypertension, we investigated the relationship between the antihypertensive action of delapril, a newly developed converting enzyme inhibitor (CEI), and its effects on vascular angiotensin II (Ang II) release in spontaneously hypertensive rats (SHR). Male SHRs were given delapril or its active metabolite (5-hydroxydelapril diacid; 5-hydroxy-DPD) orally (10 mg/kg/day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was directly determined by extraction with Sep-Pak C18 cartridges connected to the perfusion system. Both delapril and 5-hydroxy-DPD produced a sustained antihypertensive action. The spontaneous release of Ang II from isolated perfused hind legs of control SHRs was about 50 to 110 pg during the first 30 min of perfusion, and it remained stable up to 3 h. Another active metabolite, delapril diacid (DPD), when added to the perfusion medium (10(-9) to 5 x 10(-5) mol/L), suppressed the Ang II release in a dose-dependent manner. The maximal percent inhibition of Ang II released evoked by DPD (5 x 10(-6) mol/L) was approximately 51%. Oral pretreatment of either delapril or 5-hydroxy-DPD for 2 weeks suppressed the Ang II release by 61% and 73% for delapril and 5-hydroxy-DPD, respectively. These results suggest the presence of a functional RAS in vascular tissues, and that delapril exerts its antihypertensive effect through inhibition of vascular Ang II release in SHRs.

Administration, Oral↗
PubMed1991

Direct proof for local generation and release of angiotensin II in peripheral human vascular tissue.

Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused human umbilical veins was inhibited by the angiotensin-converting enzyme inhibitor captopril. To further investigate the mechanism by which Ang II is generated in the blood vessels of humans, we examined the effects of various inhibitors of the renin-angiotensin system (captopril, delapril, N-acetyl-pepstatin, and human renin inhibitor KRI-1314) on Ang II release from perfused human umbilical cord veins in vitro. Isolated human umbilical veins were perfused with Krebs-Ringer solution, and immunoreactive Ang II released into the perfusate was measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Both captopril and delapril diacid (10(-9) to 5 x 10(-6) mol/L), an active metabolite of delapril hydrochloride, suppressed the Ang II release in a dose-dependent fashion; the maximal percent suppression of Ang II release evoked by these inhibitors (5 x 10(-6) mol/L) was 56% and 64%, respectively, for captopril and delapril. Both N-acetyl-pepstatin (10(-9) to 10(-5) mol/L) and KRI-1314 (10(-9) to 10(-6) mol/L) suppressed Ang II release in a dose-related manner. At a 10(-6) mol/L concentration, KRI-1314 produced a 74% reduction in the basal rate of Ang II release, and a reduction threefold greater than the maximal reduction in basal Ang II release produced by N-acetyl-pepstatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Effect of delapril on the vascular angiotensin II release in isolated hind legs of the spontaneously hypertensive rat: evidence for potential relevance of vascular angiotensin II to the maintenance of hypertension.

1. In view of a recent interesting hypothesis that the vascular renin-angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar-Kyoto strain (WKY). 2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep-Pak C18 cartridges connected to the perfusion system. 3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9 +/- 17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5 +/- 9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose-dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR. 4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.

Angiotensin II↗
PubMed1991

Attenuated release of atrial natriuretic factor due to sodium loading in salt-sensitive essential hypertension.

Forty-one patients with essential hypertension were classified as salt-sensitive (SS) or non-salt-sensitive (NSS) from the changes in mean blood pressure (MBP) with alterations in sodium intake from 35 mmol (low-sodium) to 250 mmol/day (high-sodium). Whereas there was no difference in plasma levels of atrial natriuretic factor (ANF) on a normal-sodium diet (120 mmol) between the 2 groups, the degree of increase in the plasma ANF level between the low- and high-sodium intake was significantly greater in NSS than in SS (p less than 0.001). In addition, the urinary sodium excretion on a high-sodium diet was smaller in SS than in NSS. There was a significant positive correlation between the plasma ANF and MBP after the high-sodium intake in both SS (r = 0.67, p less than 0.01) and NSS (r = 0.60, p less than 0.01); however, the relation of plasma ANF to MBP shifted apparently to a lower level in SS compared with NSS. These findings not only indicate that there exists a hyporesponsiveness of ANF release by the heart of SS patients in response to high-sodium loading, but also imply that such a response contributes to blood pressure-elevating mechanisms due to sodium loading in this type of human hypertension.

Adult↗
PubMed1991

[Release of endothelin from isolated perfused human umbilical vein. I: Effect of ionomycin].

Endothelin-like immunoreactivity (ET-LI) was directly measured in the perfusate from the isolated human umbilical vein perfused with Krebs-Ringer solution. The identity of the immunoreactive peptide was confirmed as ET-1 by high-performance liquid chromatography. The rate of release of ET-LI was 86.7 +/- 25.9 (SE) fmol during the first perfusion period of 30 min, and it remained stable at least for 4 hours. Calcium ionophore ionomycin, added to the perfusion medium (10(-7)-10(-6) M), stimulated the ET-LI release in a dose-dependent fashion; it increased the rate of release by 29.1% and 143.4% over the control at the concentrations of 10(-7) and 10(-6) M, respectively. These results taken together with previous observations of synthesis of ET in cultured vascular endothelium provide direct evidence for local generation and subsequent release of ET from vascular beds of human beings.

Calcium↗
PubMed1990

Effect of delapril hydrochloride on angiotensin II release from isolated rat hind legs.

The effect of the newly developed angiotensin-converting enzyme (ACE) inhibitor, delapril hydrochrolide (CV-3317), on the release of immunoreactive angiotensin II (irAng II) from isolated rat hind legs was compared with that of captopril. Both ACE inhibitors, added to the perfusion medium (2 X 10(-9) - 10(-6) M), suppressed irAng II release in a dose-dependent manner, but the inhibition was greater with delapril than with captopril. The results provide further support for the concept that vascular tissues produce Ang II and release it in a regulated fashion. The results also suggest a possible link between the antihypertensive mechanism of ACE inhibitors, including delapril, and the suppression of vascular Ang II release.

Angiotensin II↗
PubMed1989

Direct evidence for local generation and release of angiotensin II in human vascular tissue.

A direct measurement of both angiotensins I and II immunoreactive substances was made in the perfusate from isolated human umbilical vein perfused with Krebs-Ringer solution which was free of any component of the renin-angiotensin system. The identity of the immunoreactive peptides was confirmed as angiotensin I and angiotensin II by high-performance liquid chromatography in reference to standard compounds. The rate of release of angiotensins was 41.9 +/- 7.4 and 63.4 +/- 12.0 pg for angiotensins I and II, respectively, during the first perfusion period of 30 min, and it remained stable at least for 3 hours. Angiotensin-converting enzyme inhibitor captopril, added to the perfusion medium (10(-9) to 5 x 10(-6) M), suppressed immunoreactive angiotensin II release in a dose-dependent fashion; the maximal percent inhibition of angiotensin II release evoked by captopril (5 x 10(-6) M) was approximately 56%. These results taken together with the previous observations of presence of essential components of the renin-angiotensin system in vascular tissue provide direct evidence for local generation and subsequent release of angiotensin II in vascular beds of human beings.

Angiotensin I↗
PubMed1989

Atrial natriuretic factor (ANF) increases urinary protein excretion in patients with essential hypertension: a possible role of ANF for renal handling of protein.

Low dose iv infusion (0.01 and 0.03 micrograms/kg per min, for 30 min each) of alpha-human atrial natriuretic factor (alpha-hANF) produced a significant increase (+300%) in urinary protein excretion in patients with essential hypertension but not in normotensive controls, when their renal function was normal. The major component of excreted proteins induced by alpha-hANF infusion was presumed to be albumin on the basis of molecular weight (69,000) analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Urine output and sodium and potassium excretion rates were increased dose-dependently by alpha-hANF infusion in the hypertensive patients in a similar fashion to those in the controls. Glomerular filtration rate (GFR) remained unchanged in the controls but was slightly increased in the patients (+33%) during the infusion. These results suggest that besides its previously recognized physiological functions such as natriuresis and diuresis, ANF plays an important role in the regulation of renal handling of proteins in patients with essential hypertension.

Adult↗
PubMed1989

Atrial natriuretic peptide in human neuroblastoma.

To clarify the presence of atrial natriuretic peptide (ANP) in neural tissue, extracts from human neuroblastoma which is considered of neural crest origin were analyzed using a specific radioimmunoassay (RIA) for ANP. High concentrations of immunoreactive ANP ranging from 2.7 to 18.4 ng per mg of protein were demonstrated in the tissue. Furthermore, high performance gel permeation chromatography (HPGPC) coupled with the RIA revealed that the immunoreactive ANP found in the tissue consisted of only one component with molecular weight of 12,000 to 13,000 daltons, corresponding to gamma-human ANP (hANP). These results could be direct evidence for generation of ANP intrinsic of human neuronal tissue, and also suggest that neuroblastoma can be used as a model for investigation of mechanism of ANP formation within the neuronal tissues.

Atrial Natriuretic Factor↗
PubMed1987

Multiple forms of immunoreactive renin in human adrenocortical tumour tissue from patients with primary aldosteronism.

There is increasing evidence which suggests that the adrenal gland contains the renin-angiotensin cycle. The localization of renin has been reported to be mainly in the zona glomerulosa rather than the fasciculata medullary portion. In the present study we have investigated extracts from aldosteronomas (n = 3), which are believed to derive from the zona glomerulosa cells. In addition, we have attempted to characterize the biochemical properties of the adrenal renin. Sizable quantities of renin-like activity (32.0 +/- 7.7 ng of angiotensin I generated h-1 mg-1 of protein, mean +/- SEM) were detected in the extracts. This renin-like activity was inhibited by anti-renin antibody raised against pure renin (mean, 95% of the total renin-like activity), indicating that it was not due to the non-specific action of proteases such as cathepsin D. The optimum pH of the tissue renin-like enzyme was 6.0 for rat plasma substrate. Differences were found, however, in the molecular mass (36,000, 37,000, 44,000 and 48,000), binding to concanavalin A and isoelectric points (4.40, 4.68 and 5.00). These results confirm the existence of specific renin in aldosteronoma. Renin microheterogeneity could be evidence for local production of the enzyme.

Adrenal Cortex Neoplasms↗
PubMed1987

Immunohistochemical demonstration of prostaglandin E-2 in preimplantation mouse embryos.

An antiserum to prostaglandin (PG) E-2 and indirect immunofluorescence were used to demonstrate immunohistochemically the presence of PGE-2 in preimplantation mouse embryos. Fluorescence was observed in the cytoplasm of unfertilized 1-cell embryos to the blastocyst stage. The strongest fluorescence was detected at the 8-cell and morula stages. In embryos cultured from the 2-cell stage on, the fluorescence was observed in the cytoplasm of 4-cell embryos to the blastocyst stage. No differences were observed in the intensity and the distribution of the fluorescence between embryos in vivo and those in vitro. However, when blastocysts were cultured in a medium containing 100 microM-indomethacin, the fluorescence was diminished markedly. We therefore suggest that preimplanted mouse embryos contain PGE-2 during their early developmental stages and that the embryos synthesize the PGE-2.

Animals↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗