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Biomedical subjects

I Nishio

Publications and source records attributed to I Nishio.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Hypertension in the patients with impaired glucose tolerance].

Diabetes mellitus is commonly associated with hypertension. Association of diabetes mellitus and hypertension predispose an individual to atherosclerotic cardiovascular disease. Hyperinsulinemia is one of the important candidates to cause hypertension in the patients with diabetes mellitus. Several mechanisms mediated by hyperinsulinemia can be entertained as follows: 1) sodium and water retention, 2) increased sympathetic nerve activity and reduced catecholamine clearance, 3) increased intracellular calcium concentration and reduced magnesium concentration, 4) increased coagulant activity and impaired fibrinolytic activity, 5) impaired endothelium-dependent NO synthesis and release, 6) increased vascular responsiveness for the vasoactive substrates, 7) increased proliferation of vascular smooth muscle cell by activation of protein kinase C or mediated by insulin and IGF-1 action.

Arteriosclerosis↗
PubMed1995

Effects of captopril on [3H]-norepinephrine release in rat central nervous system.

1. The present study was performed to investigate the effects of captopril (an angiotensin converting enzyme inhibitor, ACE-I) on noradrenergic transmission in the rat central nervous system. 2. Slices of rat hypothalamus and medulla oblongata were prepared and prelabelled with [3H]-norepinephrine. Slices were continuously superfused with Krebs-Ringer solution, and electrical stimulation (1 Hz) was performed. 3. Captopril significantly inhibited the stimulation-evoked [3H]-norepinephrine release from rat hypothalamic slices in a dose-dependent manner (S2/S1 ratio: control 0.904 +/- 0.025, n = 6, captopril 1 x 10(-5) mol/L 0.617 +/- 0.043, n = 6, P < 0.05, captopril 5 x 10(-5) mol/L 0.547 +/- 0.037, n = 6, P < 0.05). However, the basal release of [3H]-norepinephrine was not affected by captopril. 4. Captopril also reduced the stimulation-evoked [3H]-norepinephrine release in the medulla oblongata (S2/S1 ratio: control 0.878 +/- 0.018, n = 6, captopril 3.3 x 10(-5) mol/L 0.624 +/- 0.046, n = 6, P < 0.05). 5. These results show that captopril might inhibit the stimulation-evoked norepinephrine release in rat hypothalamus and medulla oblongata. Although the precise mechanisms underlying the neurosuppressive effect of captopril are still uncertain, the finding suggests that the inhibition of noradrenergic transmission might be related to the central action of the ACE-I.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Increased calcium sequestration by sarcoplasmic reticulum in small muscular arteries in young spontaneously hypertensive rats.

1. Sarcoplasmic reticulum (SR) in small resistance arteries plays a role in the regulation of the cytosolic free calcium concentration by sequestration of calcium from cytoplasm. 2. To examine the contribution of calcium (Ca2+) sequestration by the SHR to both contraction and relaxation in young spontaneously hypertensive rats (SHR), we measured evoked tension before and after depletion of SR Ca2+ stores in the rings of the first branch of superior mesenteric artery in 5 week old SHR and age-matched Wistar-Kyoto (WKY) rats. Contractile responses were induced by 40 mmol/L potassium and 10 mmol/L caffeine before and after the treatment with ryanodine or thapsigargin, which depletes SR calcium stores. 3. The magnitude of potassium-induced contraction was almost the same in both strains. 4. Ryanodine and thapsigargin did not affect the resting tension and almost decreased caffeine-induced contraction in both strains. 5. After the treatment with ryanodine or thapsigargin, the magnitude and the rate of potassium-induced contraction were augmented greatly in SHR, but not in WKY. 6. The relative relaxation rate after exposure of potassium was significantly slowed in SHR by ryanodine or thapsigargin, but only slightly in WKY. 7. These results suggest that Ca2+ sequestration by the SR in SHR was greater than in WKY. Therefore, it is concluded that SR plays an important role in preventing the development of hypertension in SHR via a buffering effect on the elevation of cytosolic free Ca2+.

Animals↗
PubMed1995

Spin-labelling study of biomembranes in spontaneously hypertensive rats: calcium- and calmodulin-dependent regulation.

1. The present study was performed to investigate alterations in membrane characteristics of spontaneously hypertensive rats (SHR) by using an electron paramagnetic resonance (EPR) and spin-labelling methods. 2. Washed erythrocytes from SHR were examined and compared with erythrocytes from age-matched normotensive Wistar-Kyoto (WKY) rats. 3. The values of outer hyperfine splitting (2T' 11) and that of the order parameter (S) obtained from EPR spectra for a spin label agent (5-nitroxide stearate) were significantly higher in the erythrocytes of SHR than in those of WKY rats. 4. When calcium (Ca2+) was loaded to erythrocytes with a Ca2+ ionophore (A 23187), the order parameter (S) of the EPR spectra showed a greater increase in SHR than in WKY rats. Furthermore, the Ca2+ -induced change in the order parameter (S) of SHR was significantly antagonized by pretreatment of the Ca2+ antagonists (verapamil, diltiazem) and a calmodulin antagonist (W-7). 5. The results show that the erythrocyte membranes of SHR tolerated different spin motions from those of normotensive WKY rats in the EPR study, which might be associated with the idea that the membrane fluidity might be lower in SHR. Furthermore, the data suggest that Ca2+ -calmodulin antagonists may ameliorate the Ca2+ -induced changes in membrane functions in hypertension.

Animals↗
PubMed1995

Altered production of nerve growth factor in cultured vascular smooth muscle cells from genetically hypertensive rats.

1. Nerve growth factor (NGF) is a neurotrophic peptide for peripheral sympathetic nerves. Hypotrophy of sympathetic nerve ganglia and reduced content of neuropeptide Y were reported in genetically hypertensive (GH) rats. These facts led us to consider that production of NGF might be altered in GH rat cells. 2. Vascular smooth muscle cells (VSMC) were prepared from the aortic media of 12 week old GH rats and age-matched normotensive (NT) rats by enzyme digestion method. Growth rates and the maximum cell densities were fairly equivalent between GH cells and NT cells. 3. The NGF content in the medium was measured using an enzyme immunoassay against mouse beta NGF. The amount of NGF secreted from VSMC of GH were 1.2 pg/10(4) cells per 48 h in the progressive phase and 0.7 pg/10(4) cells per 48 h in the quiescent phase, while those of NT were 8 pg/10(4) cells per 48 h and 1 pg/10(4) cells per 48 h, respectively. The levels of NGF secretion per cells were greater in NT cells. In summary, NGF secretion from VSMC were reduced in GH. 4. These results suggested that a reduced production of NGF from VSMC might be involved in the reported hypotrophy of sympathetic nerve cells in GH.

Animals↗
PubMed1995

Synergistic effects of Bay K 8644 and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats.

1. In the present study, we examined the effects of Bay K 8644, a dihydropyridine (DHP)-sensitive Ca2+ channel agonist, and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats (SHR). 2. In the preliminary studies using Sprague-Dawley rats, Bay K 8644 by itself had no significant effects on the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release in a dose-related fashion. The facilitatory effects of bradykinin on norepinephrine release were potentiated by Bay K 8644. 3. In SHR, Bay K 8644 significantly increased the stimulation-evoked norepinephrine release from hypothalamic slices. However, exposure of slices to Bay K 8644 caused no significant effects on norepinephrine release in Wistar-Kyoto (WKY) rats. The effects of Bay K 8644 in combination with bradykinin on the stimulation-evoked norepinephrine release were also greater in SHR than in WKY rats. 4. These results demonstrate that Bay K 8644 significantly potentiated the facilitatory effects of bradykinin on norepinephrine release in rat hypothalamus. The finding indicates a possible interaction of bradykinin with DHP-sensitive Ca2+ channels in the central nervous system. Furthermore, the pronounced effects of Bay K 8644 and bradykinin in SHR suggest that bradykinin-related Ca2+ channels might have a role in the regulation of norepinephrine release in the hypothalamus of SHR.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Role of protein kinase C in relationship between Ca2+ and contractile elements in rat alpha-toxin-permeabilized mesenteric artery.

Phorbol ester, which activates protein kinase C (PKC), modulates vasoconstrictor-induced tension in vascular smooth muscle. Recently, Staphylococcal aureus alpha-toxin, which produces too small pores in the plasma membrane to allow passage of proteins, such as PKC, is used to investigate the signal transduction system in vascular smooth muscle cells. In order to elucidate the role of PKC on vascular smooth muscle contraction, we examined whether PKC activation influences the relationship between intracellular Ca2+ ([Ca2+]i) and tension in Wistar rat superior mesenteric artery (SMA) using vascular smooth muscle permeabilized with Staphylococcal alpha-toxin. [Ca2+]i was clamped at specified values (10(-8.5)-10(-4) mol/L) using EGTA-Ca2+ buffer. In alpha-toxin non-treated rings of SMA, isometric tension was evoked by 10 mmol/L caffeine and 10-30 mmol/L external potassium (high K+) in the absence or presence of phorbol 12, 13-dibutyrate (PDBu), a PKC activator, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), and staurosporine (PKC inhibitors). PDBu significantly augmented caffeine- and high K(+)-evoked contractions. H-7 and staurosporine significantly attenuated caffeine- and high K(+)-evoked contractions augmented by PDBu. Moreover, H-7 significantly suppressed high K(+)-induced contraction in the absence of PDBu. In alpha-toxin permeabilized artery, PDBu shifted the [Ca2+]i-force relationship curve to the left. These results suggest that PKC activates vascular smooth muscle contraction by increasing the sensitivity of the contractile apparatus to Ca2+.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

DA1 receptor-mediated renin release from isolated rat glomeruli.

The present study was performed in order to examine the effects of dopamine (DA) on renin release and to clarify which subtype of DA receptor, DA1 or DA2 contributes to renin release. Male Wistar rats aged seven weeks were used. Glomeruli were isolated by the modified Beierwaltes' sieving method and were transferred to a sealed chamber and superfused with Krebs-Ringer solution. In the first experiment, the changes in renin release induced by DA and the effects of a non-selective DA antagonist, haloperidol and a beta antagonist, propranolol on DA-induced renin release were examined. In the second experiment, the effect of a DA2 receptors antagonist, spiperone and of a DA1 receptor antagonist, SCH-23390 on renin release were investigated. Basal levels of renin release were 2.46 +/- 0.36 ng ATI/h/10(4) glomeruli (mean +/- SEM). DA caused a dose-dependent increase in renin release. The renin release induced by DA was inhibited by haloperidol but not by propranolol. The maximum level of renin release induced by 10(-5)M DA was 4.13 +/- 0.63 ng ATI/h/10(4) glomeruli. SCH-23390 at 10(-5)M caused significant suppression of DA-induced renin (p < 0.05). In contrast, 10(-5)M spiperone failed to suppress DA-induced renin release. These results suggest that DA induced renin release from isolated glomeruli through the DA1 receptors.

Adrenergic beta-Antagonists↗
PubMed1995

[Assessment of right ventricular function by magnetic resonance imaging of old myocardial infarction].

The usefulness of magnetic resonance imaging (MRI) for estimating right ventricular function and the influence of left ventricular dysfunction on the performance of the right ventricle were assessed in 43 patients with chronic myocardial infarction (MI) and 14 control subjects (N) using electrocardiography-gated MRI and cardiac catheterization. Patients with MI were divided into three groups according to the location of the coronary lesions; 22 patients with left coronary artery lesion (LCA group), 13 with right coronary artery lesion (RCA group), and 8 with both left and right coronary artery lesions (L+R group). The right ventricular end-diastolic volume (RVEDV) and right ventricular ejection fraction (RVEF) were measured by Simpson's rule algorithm on transverse images of the right ventricle obtained at the end-systolic and end-diastolic phases. In 34 of the 43 patients, the same parameters of right ventricular function were calculated by the thermodilution method using a Swan-Ganz catheter with rapid response thermistor. Left ventricular ejection fraction (LVEF) and end-diastolic volume were determined from left ventriculography. The intraobserver reproducibility (11 cases, r = 0.97) and interobserver reproducibility (11 cases, r = 0.92) of RVEF measured by MRI were excellent. The RVEF and RVEDV determined from MRI were significantly correlated with those from the thermodilution method (RVEF: r = 0.56, RVEDV: r = 0.52). There was no difference in right ventricular end-diastolic volume index in any patient group. The RVEF was decreased in the L+R (41.0 +/- 4.5%, p < 0.01) and RCA (45.9 +/- 6.6%) groups, but there was no difference between the LCA (50.6 +/- 6.6%) and N (48.9 +/- 4.3%) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Mutation of low affinity nerve growth factor receptor gene in spontaneously hypertensive and stroke-prone spontaneously hypertensive rats: one of the promising candidate genes for hypertension.

There is evidence that abnormal formation of the sympathetic nervous system might be important for pathogenesis of hypertension. In the present study we analyzed nucleotide sequences of low affinity nerve growth factor receptor (LNGFR) genes in the spontaneously hypertensive rat and its stroke-prone substrain. There was a point mutation generating an amino acid substitution in signal peptide of these LNGFRs. This result suggested that the mutated LNGFR gene is one of the promising candidate genes for hypertension.

Amino Acid Sequence↗
PubMed1994

Efficacy of inhaled nitric oxide in a porcine model of adult respiratory distress syndrome.

OBJECTIVE: To assess the efficacy of inhaled nitric oxide (NO) in reducing pulmonary hypertension in a porcine model of adult respiratory distress syndrome. DESIGN: Nonrandomized, controlled experiment without blinding. SETTING: Surgical research laboratory. PARTICIPANTS: Twelve pigs, matched equally for body weight. INTERVENTION: Acute lung injury was induced by intravenous injection of oleic acid. Animals were then divided into either a control group, for monitoring without any further intervention, or a NO-treatment group, in which NO was administered at concentrations of 10 to 80 ppm, with each step separated by a NO-free interval to assess duration of effect. MAIN OUTCOME MEASURES: Pulmonary artery pressure, systemic blood pressure, PaO2, intrapulmonary shunt fraction, and extravascular lung water. Nitrosylated hemoglobin, arterial methemoglobin, and plasma nitrite and nitrate concentrations. RESULTS: All animals responded to oleic acid injection with rapid development of pulmonary hypertension and deterioration of PaO2 and intrapulmonary shunt fraction. Inhaled NO reversed these changes in a concentration-dependent manner. Cessation of NO administration led to a prompt return of pulmonary hypertension. A small but significant drop in systemic blood pressure was observed only at the highest concentration of NO administered (80 ppm). Extravascular lung water almost doubled following oleic acid injury. This increase was sustained in all animals for the remainder of the experiment. Significant increases in circulating methemoglobin and plasma nitrite and nitrate concentrations were measured during NO inhalation. CONCLUSION: Inhaled NO appears to be a selective pulmonary vasodilator and may prove to be useful in improving gas exchange in adult respiratory distress syndrome.

Administration, Inhalation↗
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↗