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Biomedical subjects

Y Masuyama

Publications and source records attributed to Y Masuyama.

At least 55 records · Page 3Linked to original sources
PubMed1994

Deficient activity of stimulatory nucleotide-binding regulatory protein in lymphocytes from patients with essential hypertension.

Lymphocytes are widely used as a model for the cardiovascular beta-adrenoceptor-adenylate cyclase system. We evaluated the role of this system in the pathogenesis of hypertension by studying lymphocytes obtained from patients with essential hypertension. Untreated hypertensive patients and normotensive control subjects were studied. The number and affinity of the beta-adrenoceptors were measured by a radioligand binding method with 125I-cyanopindolol. The responses of cyclic adenosine monophosphate (cAMP) to isoproterenol, cholera toxin, and forskolin were also determined. The concentration and affinity of beta-adrenoceptors did not differ significantly in the two groups, nor was a significant difference found in the basal level of cAMP. The effects of isoproterenol on the accumulation of cAMP were reduced in the lymphocytes from the hypertensive compared with the normotensive subjects. There was no significant difference in the effect of forskolin on cAMP accumulation in the two groups. These results indicate that the activity of the stimulatory nucleotide binding regulatory protein (Gs-protein) is reduced in lymphocytes from patients with essential hypertension. This defect of Gs-protein in the lymphocytes may represent a defect of Gs-protein in the cardiovascular system in such patients.

Adenylyl Cyclases↗
PubMed1994

Effect of temocapril on haemodynamic and humoral responses to exercise in patients with mild essential hypertension.

1. This study was carried out to evaluate the effect of temocapril on haemodynamic and humoral responses to exercise in nine patients with mild essential hypertension (WHO stages I and II). 2. After a 4-week placebo period, temocapril was administered at a dose of 1.0 mg once daily for 2-4 weeks. Graded submaximal bicycle ergometer exercise was performed before and after temocapril treatment, and the changes in arterial blood pressure, heart rate, cardiac output (CO), and systemic vascular resistance (SVR) were evaluated. In addition, the plasma norepinephrine (NE) level was determined both at rest and peak exercise before and after temocapril treatment. 3. Both the systolic and diastolic blood pressure were reduced at rest and during exercise by temocapril treatment. No significant change in the resting heart rate and CO was observed, and the exercise-induced increase of these parameters was also not affected by temocapril. In contrast, the resting SVR was significantly decreased by temocapril, although the exercise SVR was similar during both temocapril and placebo treatment. 4. Although there was no significant change in the plasma NE level with temocapril treatment, the exercise-induced increase of plasma NE was significantly suppressed by temocapril. 5. These results indicate that temocapril reduces the blood pressure without causing any significant changes in the heart rate and CO at rest, and that it does not produce any changes in the haemodynamic response to exercise.

Adult↗
PubMed1994

Inhibitory effects of verapamil on [3H]-acetylcholine release in the central nervous system of Sprague-Dawley rats.

1. The purpose of the present study was to investigate the effects of verapamil, a Ca2+ channel blocker, on acetylcholine (ACh) release in the CNS. 2. Striatal slices of rats, prelabelled with [3H]-ACh, were superfused with Krebs'-Ringer solution. The slices were stimulated by electrical pulses (1 Hz) or by an excitatory amino acid, L-glutamate and the effects of verapamil on the release of ACh were examined. 3. Electrical stimulation produced an increase in [3H]-ACh release from the striatal slices. Exposure of the slices to verapamil significantly inhibited the stimulation-evoked [3H]-ACh release. 4. An endogenous excitatory amino acid, L-glutamate, also elicited the release of [3H]-ACh. Verapamil significantly reduced the L-glutamate-induced release of [3H]-ACh and the inhibitory effect of verapamil was more pronounced in the presence of Mg2+ in the medium. 5. The results of the present study demonstrate that verapamil inhibited both electrically- and chemically-stimulated [3H]-ACh release from the rat striatum. The inhibition of cholinergic transmission by verapamil might be related to the central effect of the Ca2+ channel blocker.

Acetylcholine↗
PubMed1994

Effects of diltiazem on [3H]-acetylcholine release in rat central nervous system.

1. In the present study, we examined the effects of a Ca2+ channel blocker, diltiazem, on [3H]-acetylcholine (ACh) release in the rat CNS. 2. Diltiazem inhibited the electrically stimulated [3H]-ACh release in a dose-related fashion striatal slices of Sprague-Dawley (SD) rats. The basal release of [3H]-ACh was not significantly affected by diltiazem except at a high concentration. 3. The stimulation-evoked [3H]-ACh release was not different between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. 4. The inhibitory effect of diltiazem on the stimulation-evoked [3H]-ACh release was significantly greater in SHR than in WKY rats. 5. The results show that diltiazem inhibited the stimulation-evoked ACh release in the rat CNS. The pronounced effect of diltiazem in SHR suggests that the inhibition of central cholinergic activity might contribute, at least partially, to the hypotensive mechanisms of the Ca2+ channel blocker.

Acetylcholine↗
PubMed1994

Determination of delta-aminolevulinic acid in plasma using high-performance liquid chromatography: a sensitive indicator of lead effects.

We developed a simple and reliable method for determining delta-aminolevulinic acid (ALA) in plasma (ALA-P) by fluorometric high-performance liquid chromatography. The method was applicable to 100 microliters of plasma and the mean +/- standard deviation for analytical recovery was 100.4 +/- 2.6% when 50 micrograms/l of ALA was added to 14 plasma samples. The detection limit for ALA-P was 2.0 micrograms/l (signal-to-noise ratio was 5) and the standard curve was linear in a wide range up to 400 micrograms/l. The ALA-P level for 26 unexposed male adults was 8.6 +/- 1.3 micrograms/l. In 72 male lead workers, logarithm of ALA-P concentration was significantly correlated with blood lead concentrations (Pb-B) of 2.5-115.4 micrograms/dl (r = 0.924, p < 0.001). Even at the Pb-B level less than 15 micrograms/dl, significant linear relationships were found between Pb-B and log ALA-P (r = 0.632, p < 0.01), between Pb-B and delta-aminolevulinic acid dehydratase activity (ALA-D) (r = -0.573, p < 0.05), and between ALA-D and ALA-P (r = -0.765, p < 0.001). It is suggested that ALA-P determined by the present method is a useful indicator of biological effects of lead, especially in the wide range of Pb-B level.

Adult↗
PubMed1994

Glutamatergic regulation of [3H]-noradrenaline release in the medulla oblongata of normotensive and spontaneously hypertensive rats.

OBJECTIVE: To assess in vitro the role of glutamate receptors in the regulation of noradrenaline release from the medulla oblongata of normotensive and hypertensive rats. DESIGN AND METHODS: The effects of L-glutamate (an endogenous ligand for glutamate receptors), glycine (an allosteric agonist for the N-methyl-D-aspartate type of glutamate receptors) and MK-801 (an antagonist for N-methyl-D-aspartate receptors) on [3H]-noradrenaline release were examined in slices of rat medulla oblongata. RESULTS: L-Glutamate elicited [3H]-noradrenaline release from slices of rat medulla oblongata in magnesium-free medium. Glycine also increased the release of noradrenaline. Moreover, the effect of L-glutamate on noradrenaline release was significantly potentiated by glycine. MK-801 inhibited the increase in noradrenaline release evoked by L-glutamate. In spontaneously hypertensive rats (SHR) the facilitatory effect of L-glutamate on noradrenaline release was significantly more pronounced than in Wistar-Kyoto (WKY) rats. Furthermore, glycine alone and in combination with L-glutamate increased the noradrenaline release to a greater extent in SHR than in WKY rats. CONCLUSION: The present results show that the excitatory amino acids might increase noradrenaline release from rat medulla oblongata, which was partially dependent on the N-methyl-D-aspartate type of glutamate receptors. The greater effect of L-glutamate and glycine in SHR suggests that these amino acids might be involved in the regulation of noradrenaline release in the medulla oblongata of hypertension.

Animals↗
PubMed1993

Determination of urinary alkoxyacetic acids by a rapid and simple method for biological monitoring of workers exposed to glycol ethers and their acetates.

In control subjects and workers exposed to glycol ethers and their acetates, we determined the urinary metabolites (three alkoxyacetic acids) by a simple and rapid method. Levels of urinary metabolites were significantly higher in the solvent workers than in the nonexposed subjects. The exposure levels measured by personal monitoring of breathing zone air were far below the threshold limit value. The present results indicate that determination of urinary alkoxyacetic acids by the practical method used here is useful for evaluating excessive exposure to solvents.

Acetates↗
PubMed1993

Effects of neurotensin on norepinephrine release in blood vessels of spontaneously hypertensive rats.

The present study was performed to investigate the effects of neurotensin on noradrenergic transmission in blood vessels of hypertension. In the perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats, we examined the influences of neurotensin on vascular responsiveness and norepinephrine release from adrenergic neurons. In studies with male standard Wistar rats, endogenous norepinephrine release during periarterial nerve stimulation was inhibited by neurotensin in a dose-dependent manner. Vasoconstrictor responses to electrical nerve stimulation were also inhibited by neurotensin. In SHR, the stimulation-evoked pressor responses and norepinephrine release were enhanced compared with WKY rats. The suppression of these responses by neurotensin was significantly less in SHR than in WKY rats. These results show that neurotensin could have a modulatory effect on noradrenergic activity and cause a decrease in stimulation-evoked norepinephrine release from vascular adrenergic neurons. The lesser reduction of pressor responses and norepinephrine release by neurotensin in SHR might suggest an insufficient regulation of vascular adrenergic transmission by the peptide hormone in hypertension.

Adrenergic Fibers↗
PubMed1993

Production of nerve growth factor by cultured vascular smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVE: Nerve growth factor (NGF) is a neurotrophic protein which acts on peripheral sympathetic nerves. Elevated NGF in vascular tissues of young spontaneously hypertensive rats (SHR) has been reported. The aim of the present study was to compare the amount of NGF secreted from cultured vascular smooth muscle cells (VSMC) and mesenteric artery and thoracic aorta segments from SHR and Wistar-Kyoto (WKY) rats. METHODS: VSMC prepared by the enzyme digestion method from the thoracic aortic media of 14-week-old SHR and age-matched WKY rats were subcultured in Dulbecco's modified Eagle's medium containing 10% fetal calf serum. Segments of mesenteric artery and thoracic aorta from 4-week-old SHR and age-matched WKY rats were similarly cultured. The NGF content in conditioned medium was measured using an enzyme immunoassay. The protein content of VSMC was measured by the Lowry method. RESULTS: Total NGF content in the cell culture medium was increased during an exponential growth phase and then gradually decreased during a quiescent phase in both rat strains. There were no significant differences in the levels of NGF secreted from mesenteric artery and thoracic aorta segments between the SHR and WKY rats. The differences in cellular protein content between SHR and WKY rats were very small. CONCLUSIONS: In contrast to the reports of increased NGF in SHR tissues, our data demonstrate that NGF secretion was lower in VSMC from SHR, and was equivalent in mesenteric artery and thoracic aorta segments from SHR and WKY rats. We have no clear explanation for these observations, but the present results indicate that upregulation of NGF in SHR tissues is not responsible for a simple enhancement of NGF synthesis in VSMC, and suggest a breakdown of the regulatory mechanism or mechanisms of NGF gene expression in SHR tissues.

Animals↗
PubMed1993

Effects of verapamil and diltiazem on dopamine release in the central nervous system of spontaneously hypertensive rats.

1. The purpose of the present study was to investigate the effects of Ca(2+)-antagonists (verapamil and diltiazem) on dopamine release in the central nervous system in hypertension. 2. Striatal slices obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were prelabelled with [3H]-dopamine, and superfused with Krebs-Ringer solution in vitro. The slices were stimulated electrically at a frequency of 1 Hz. 3. Stimulation-evoked release of [3H]-dopamine from striatal slices was significantly decreased in SHR compared with WKY rats. 4. Exposure of slices to verapamil and diltiazem significantly increased the stimulation-evoked [3H]-dopamine release. The facilitatory effects of the Ca(2+)-antagonists on dopamine release were significantly greater in SHR than in WKY rats. 5. Because central nervous system dopaminergic mechanisms appear to be depressor, the results suggest that the pronounced effects of verapamil and diltiazem on dopamine release in SHR might be involved in the central hypotensive mechanisms of the Ca(2+)-antagonists.

Animals↗
PubMed1993

Effects of bradykinin on [3H]-norepinephrine release in rat hypothalamus.

1. We examined the regulatory actions of bradykinin on norepinephrine release in the hypothalamus of rats. 2. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner (1 Hz: S2/S1 ratio, mean +/- s.e.m., control 0.868 +/- 0.016, n = 6; bradykinin 1 x 10(-6) mol/L 1.039 +/- 0.018, n = 6, P < 0.05; bradykinin 3.3 x 10(-6) mol/L 1.130 +/- 0.064, n = 6, P < 0.05). The basal release of [3H]-norepinephrine was not affected by the peptide. 3. Bay K 8644, a dihydropyridine-sensitive calcium channel agonist, significantly potentiated the facilitatory effect of bradykinin on norepinephrine release, although Bay K 8644 by itself had no significant effect. By contrast, nicardipine, a dihydropyridine-sensitive calcium channel blocker, reversed the increase in norepinephrine release induced by bradykinin and Bay K 8644. 4. These results indicate that bradykinin may increase norepinephrine release in rat hypothalamus, partially mediated by interactions with dihydropyridine-sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Effects of nicardipine on the release of acetylcholine in the rat central nervous system.

Recent studies have indicated that specific dihydropyridine-sensitive Ca2+ channel binding sites are present in the brain, and that they play a crucial role in synaptic function. The present study was performed to determine the effects of nicardipine, a dihydropyridine-sensitive Ca2+ channel blocker, on the release of acetylcholine in the rat central nervous system. Striatal slices of rats which had been prelabelled with [3H]acetylcholine were superfused with Krebs-Ringer solution. The slices were stimulated with either electrical pulses (1 Hz) or an excitatory amino acid, L-glutamate, and the effects of nicardipine on the release of acetylcholine were examined. Electrical stimulation produced an increase in [3H]acetylcholine release from the striatal slices. Exposure of the slices to nicardipine significantly inhibited the stimulation-evoked [3H] acetylcholine release. An endogenous excitatory amino acid, L-glutamate, also elicited release of [3H]acetylcholine. Nicardipine significantly reduced the L-glutamate-induced release of [3H]acetylcholine, and the effect was pronounced in the presence of Mg2+. These results demonstrate that nicardipine inhibits both electrically and chemically stimulated [3H]acetylcholine release from rat striatum. The ability of nicardipine to inhibit cholinergic transmission may be related to the central effect of this Ca2+ channel blocker.

Acetylcholine↗
PubMed1993

[Usefulness of delta-aminolevulinic acid in blood as an indicator of lead exposure].

The concentration of delta-aminolevulinic acid in blood (ALA-B) was determined using high performance liquid chromatography (HPLC). To improve the chromatographic separation and the recovery rate of ALA determination in blood, acetate buffer was used in the reaction mixture of fluorescence derivatization. The detection limit of ALA-B was ca. 2 micrograms/l at signal to noise ratio of 5, and the analytical recovery was 102.0 +/- 4.10% (mean +/- SD), when 50 micrograms/l of ALA was added to 7 blood samples (ALA-B levels: 6.5-103.0 micrograms/l). ALA-B levels in control subjects (n = 19) were 5.3 +/- 1.4 micrograms/l (mean +/- SD) and those in 52 lead workers (blood lead levels (Pb-B): 2.4-86.2 micrograms/dl) were 15.4 +/- 12.2 micrograms/l (range: 3.1-137.3 micrograms/l). Standard curve of ALA was linear over a wide range, at least up to 400 micrograms/l. In the workers, the correlation coefficients of ALA-B vs. Pb-B and ALA-B vs. delta-aminolevulinic acid dehydratase activity (ALA-D) were higher than those of urinary concentration of ALA vs. Pb-B and that vs. ALA-D, especially in the moderate Pb-B level (less than 40 micrograms/dl, n = 35). Unless the urinary concentrations of ALA were not corrected, significant correlation could not be found between Pb-B and urinary ALA in the workers moderately exposed to lead, and the correlation coefficient between urinary ALA and ALA-D was -0.354, while the correlation coefficients of ALA-B vs. Pb-B and ALA-B vs. ALA-D were 0.739 and -0.746, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗
PubMed1993

Membrane fluidity of erythrocytes and its modulation by ouabain in essential hypertension--an electron paramagnetic resonance study.

The purpose of the present study was to examine alterations in membrane fluidity of erythrocytes in essential hypertension by means of an electron paramagnetic resonance (EPR) and a spin labeling method. In addition, we investigated the effects of ouabain on the fluidity of erythrocytes, and elucidated a possible role of Na+, K(+)-ATPase in the regulation of membrane fluidity in hypertension. Erythrocytes obtained from patients with essential hypertension were examined compared with those from age-matched normotensive subjects. The EPR spectra for 5-nitroxide stearate incorporated into erythrocyte membranes were studied. The values of the outer hyperfine splitting and order parameter (S) of the EPR spectra were significantly higher in patients with essential hypertension than in normotensive subjects. This finding shows that the membrane fluidity of erythrocytes might be lower in essential hypertension. Ouabain-loading of erythrocytes decreased the membrane fluidity (S value was increased). The ouabain-induced changes were significantly greater in essential hypertension than in normotensive subjects. These results demonstrate that the membrane fluidity of erythrocytes might be lower in essential hypertension than in normotensive subjects. Furthermore, the membrane fluidity might be highly dependent on the Na+, K(+)-ATPase activity in essential hypertension, which would suggest an abnormality in Na(+)-related cellular functions in hypertension.

Electron Spin Resonance Spectroscopy↗
PubMed1992

Effects of verapamil on [3H]acetylcholine release in the striatum of spontaneously hypertensive rats.

In the present study, we describe the effects of Ca2+ channel antagonist (verapamil) on [3H]acetylcholine (ACh) release in the central nervous system of spontaneously hypertensive rats (SHR). The electrically stimulated release of [3H]ACh from striatal slices was not different between SHR and normotensive Wistar Kyoto (WKY) rats. Verapamil inhibited electrically stimulated [3H]ACh release in a dose-related fashion. The inhibitory effect of verapamil was significantly greater in SHR than in WKY rats. These results suggest that the Ca2+ sensitivity of central cholinergic neurons might be enhanced in SHR, which could attribute, at least partially, to the pathogenesis of hypertension.

Acetylcholine↗
PubMed1992

Facilitatory effects of diltiazem on dopamine release in the central nervous system. Focus on interactions with D2 autoreceptors and guanosine triphosphate binding proteins.

The purpose of the present study was to investigate the effects of a Ca antagonist (diltiazem) on dopamine release in the central nervous system. Rat striatal slices prelabeled with [3H]dopamine (DA) and superfused with Krebs-Ringer solution were stimulated electrically at a frequency of 1 Hz. Exposure to diltiazem (3.3 x 10(-7) to 1 x 10(-5) mol/L) significantly increased both the basal and stimulation-evoked [3H]DA release in a dose-dependent manner. Exogenously applied unlabeled DA inhibited the stimulation-evoked [3H]DA release. Diltiazem significantly antagonized the capacity of the unlabeled DA to inhibit stimulation-evoked [3H]DA release. The blockade of D2 receptors by a preferential D2 antagonist, sulpiride, reduced the facilitatory effect of diltiazem on stimulation-evoked [3H]DA release. Pretreatment with pertussis toxin, which interferes with the coupling of the inhibitory guanosine triphosphate-binding proteins to adenylate cyclase, significantly diminished the effects of diltiazem on stimulation-evoked [3H]DA release. These results show that diltiazem increased DA release in rat striatum, at least partially by interactions with the D2 autoreceptors and pertussis toxin-sensitive guanosine triphosphate-binding proteins.

Adenylate Cyclase Toxin↗
PubMed1992

Increased nerve growth factor levels in spontaneously hypertensive rats.

OBJECTIVE: Increased sympathetic innervation has been reported in spontaneously hypertensive rats (SHR); however, the precise mechanisms involved are not yet clear. Nerve growth factor (NGF), a neurotrophic peptide in peripheral sympathetic neurons, is believed to contribute to this phenomenon. METHODS: We measured the content of NGF in SHR and control Wistar-Kyoto (WKY) rats during development. Mesenteric artery, spleen, heart and sciatic nerve were isolated and homogenized. NGF content in the supernatant fractions was measured using a highly sensitive and specific two-site enzyme immunoassay. RESULTS: At 3 weeks of age, SHR had a greater NGF content in the spleen, the sciatic nerve and the mesenteric artery than WKY rats. However, these differences disappeared completely at 12 weeks of age. Cardiac NGF content was slightly lower in 3-week-old SHR and, conversely, higher in 12-week-old SHR than in age-matched WKY rats. CONCLUSIONS: These findings suggest that, except for the heart, the SHR tissues observed overproduce NGF at a young age, leading to enhancement of peripheral sympathetic nervous system activity and the production of vasoconstrictive catecholamines.

Aging↗