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Biomedical subjects

Y Nara

Publications and source records attributed to Y Nara.

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

Ultrastructural analysis of survival in cultured smooth muscle cells isolated from stroke-prone spontaneously hypertensive rats: effect of growth factors.

Our previous study in vivo suggested that vascular smooth muscle cells (VSMCs) in stroke-prone spontaneously hypertensive rats (SHRSP) were vulnerable when plasma components were deficient. Therefore, we cultured VSMCs isolated from normotensive and hypertensive rats to clarify the weakness of VSMCs isolated from hypertensive rats and maintained in plasma-deficient conditions by employing ultrastructural and biochemical analyses. VSMCs, obtained from normotensive rats and cultured without fetal bovine serum (FBS) for 1 week, were intact and well differentiated; without FBS for 2 weeks retained their original structures except for several degenerative changes. VSMCs, obtained from hypertensive rats and cultured without FBS for 2 weeks, were extensively damaged and lost their cell organelles. Apoptotic bodies were frequently observed. We also cultured VSMCs in medium containing a variety of growth factors. VSMCs obtained from normotensive rats and cultured with epidermal growth factor or insulin-like growth factor-1 for 2 weeks were almost intact, as were VSMCs from hypertensive rats, although some degenerative changes of cell organelles were observed. VSMCs from hypertensive rats, maintained with platelet-derived growth factor-BB or basic fibroblast growth factor, were generally in poor condition. Thus VSMCs from hypertensive rats have hereditary weaknesses in cell survival including apoptosis and require specific growth factors for their maintenance.

Animals↗
PubMed1996

Taurine accelerates the regression of hypercholesterolemia in stroke-prone spontaneously hypertensive rats.

The effects of taurine on the regression of pre-established hypercholesterolemia were examined in stroke-prone spontaneously hypertensive rats (SHRSP). Hypercholesterolemia was induced by feeding a hypercholesterolemic diet to SHRSP for 30 days. Then, the diet was switched to normal chow with or without 3% taurine, and the effects were followed up for another 30 days. During regression serum cholesterol level was rapidly decreased, and was accelerated by taurine. A similar accelerated decrease in cholesterol content by taurine was seen also in tissues including the liver, intestine, and aorta. In the liver, acyl-CoA:cholesterol acyltransferase (ACAT) activity was significantly low in the taurine-supplemented group, parallel with the hepatic cholesteryl ester content. On the other hand, hepatic cholesterol 7 alpha-hydoxylase activity maintained a higher level in the taurine-supplemented group. These results showed that taurine accelerates the regression of hypercholesterolemia, and suggested that this effect is related to the increase in cholesterol catabolism to bile acid through the enhancement of 7 alpha-hydoxylase activity.

Animals↗
PubMed1996

Effect of antihypertensive treatment with alacepril on insulin resistance in diabetic spontaneously hypertensive rats.

Recent clinical reports have described the close relationship between insulin resistance and hypertension. Previous reports from our laboratory documented that spontaneously hypertensive rats (SHR) have mild insulin resistance, and that this insulin resistance is more intense in SHR with diabetes induced by streptozotocin (STZ). The aim of this study was to elucidate the effects of antihypertensive treatment with alacepril on insulin resistance in these diabetic SHR. Animals were divided into four groups as follows: group A, nondiabetic SHR; group B, diabetic SHR group C, diabetic SHR treated with 0.05% alacepril; and group, D diabetic SHR treated with 0.1% alacepril. Diabetes was induced by intravenous (IV) injection of STZ (35 mg/kg bodyweight [BW]). Alacepril was given orally by mixing in laboratory chow. Mean (+/- SD) blood pressure was lowered in the alacepril-treated groups (A 212 +/- 7mm Hg and B 213 +/- 8 v C 184 +/- 6 and D 167 +/- 9; P < .01). Total integrated plasma glucose levels were different among all the groups by oral glucose tolerance test (OGTT) (B 53.6 +/- 3.3 mmol/L > C47.2 +/- 4.5 > D 42.3 +/- 1.4 > A 34.2 +/- 1.2; P < .01). Steady-state plasma glucose (SSPG during the insulin suppression test was higher in group B than in group A (15.7 +/- 1.5 mmol/L v 10.4 +/- 0.8; P < .001). The SSPG level (12.9 +/- 0.7) was significantly (P < .001) lower in group D than in untreated group B. In the diabetic groups, blood pressure was positively correlated with integrated plasma glucose (PG) (r = .79, P < .001), SSPG (r = .53, P < .02), and plasma triglyceride (r = .70, P < .001), and negatively with high-density lipoprotein (HDL)-cholesterol (r = -.74, P < .001). Alacepril treatment not only dose-relatedly lowered mean blood pressure, but also dose-relatedly improved abnormalities in carbohydrate and lipid metabolism in STZ-induced diabetic SHR. These results suggest that an angiotensin-converting enzyme inhibitor, alacepril, has an antihypertensive effect, but also improves insulin resistance in hypertension with diabetes mellitus.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Cosegregation of the new region on chromosome 3 with salt-induced hypertension in female F2 progeny from stroke-prone spontaneously hypertensive and Wistar-Kyoto rats.

1. We investigated candidate loci for salt-sensitive high blood pressure (BP) in F2 progeny from crossing Wistar-Kyoto and stroke-prone spontaneously hypertensive rats. 2. In female F2 progeny, systolic and diastolic BP on the 12th day and the seventh month after salt loading was strongly linked with the D3Mgh12 and D3Mgh6 loci on chromosome 3, respectively. 3. These loci were linked with BP only in female F2 progeny, not in males. 4. These results indicate that hormonal factors may influence salt sensitivity, particularly with respect to gender differences.

Animals↗
PubMed1996

Long-term effects of high calorie sucrose-enriched diet and streptozotocin-induced diabetes on insulin resistance in spontaneously hypertensive rats.

1. The effects of two experimental manipulations on insulin resistance were compared in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Rats were fed a high calorie sucrose-enriched diet (high calorie diet) or were made diabetic by the injection of streptozotocin (STZ). 2. After treatment with the high calorie diet for 8 weeks, blood pressure increased in SHR, but not in WKY rats. In contrast, STZ treatment decreased blood pressure in SHR, but increased it in WKY rats. 3. Plasma glucose levels during oral glucose loading were higher in SHR than in WKY rats. Glucose tolerance was impaired to a greater extent by both the high calorie diet and STZ in SHR than in WKY rats. Hyperinsulinaemia induced by the high calorie diet was severe in SHR compared with WKY rats. 4. Abnormalities in lipid metabolism induced by a high calorie diet or STZ-induced diabetes were more marked in SHR than in WKY rats. 5. Steady-state plasma glucose levels in the insulin suppression test were higher in SHR than in WKY rats, both of which were treated by either the high calorie diet or STZ. These findings indicate that insulin-stimulated glucose uptake by high calorie diet or STZ-induced diabetes was impaired to a greater extent in SHR than in WKY rats. 6. It is concluded, therefore, that SHR fed on high calorie diet or SHR with STZ-induced diabetes are suitable models to study the effects of antihypertensive treatment on glucose tolerance, insulin resistance or lipid metabolism as well as blood pressure.

Analysis of Variance↗
PubMed1996

Hypolipidemic effect of taurine in stroke-prone spontaneously hypertensive rats.

The hypolipidemic and antiatherosclerotic effects of taurine were investigated in genetically hypertensive rats: strokeprone spontaneously hypertensive rats (SHRSP). SHRSP were fed a hypercholesterolemic (HC) diet supplemented with 3% taurine for 50 days, and serum cholesterol was monitored. Cholesterol content and enzymatic activity responsible for cholesterol synthesis and metabolism were also determined in the liver, aorta, and intestine. Taurine prevented increases in the cholesterol level of the serum, liver, and aorta induced by a HC diet. Severe fat deposits of the mesenteric arteries induced by a HC diet were improved by the taurine treatment, showing the hypolipidemic and antiatherosclerotic effects of taurine. Taurine enhanced the activity of cholesterol 7 alpha-hydroxylase, a rate-limiting enzyme of bile acid synthesis, and stimulated bile acid production. These results suggest that taurine stimulates bile acid synthesis, which is closely related to the enhancement of cholesterol 7 alpha-hydroxylase activity, and thereby reduces serum cholesterol. In addition, a decrease in the intestinal acyl CoA:cholesterol acyltransferase activity by taurine suggests that the inhibition of cholesterol absorption may also be related to the hypolipidemic effect of taurine, in part.

Animals↗
PubMed1995

Peritoneal macrophages from stroke-prone spontaneously hypertensive rats accumulate more cholesteryl ester than do macrophages from Wistar-Kyoto rats.

The intracellular cholesterol metabolism of peritoneal macrophages from stroke-prone spontaneously hypertensive rats (SHRSP) was compared to that of normotensive Wistar-Kyoto rats (WKY) in order to examine the role of macrophages in the development of arterial fat deposits in the SHRSP. Scavenger receptor activity and intracellular acyl CoA:cholesterol acyltransferase (ACAT) activity were significantly higher in macrophages from SHRSP compared to findings in WKY, in the presence of modified low-density lipoprotein (LDL), acetylated-LDL (Ac-LDL). Moreover, macrophages from the SHRSP accumulated more cholesteryl ester than seen in WKY in response to Ac-LDL. ACAT activity and cholesteryl ester accumulation were inhibited by specific ACAT inhibitor, HL-004, to a similar extent, in macrophages from WKY and SHRSP. These findings suggest the susceptibility of SHRSP to arterial fat deposits.

Animals↗
PubMed1995

Hypolipidemic and antiatherosclerotic effects of a novel ACAT inhibitor, HL-004, in stroke-prone spontaneously hypertensive rats.

The hypolipidemic and antiatherosclerotic effects of a novel acyl CoA:cholesterol acyltransferase (ACAT) inhibitor, HL-004, were studied in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were administered 0.01-0.09% HL-004 mixed in a hypercholesterolemic (HC) diet for 50 days. HL-004 reduced the cholesterol and triglyceride levels in serum, as well as those in the liver, small intestine, and aorta, in a dose-dependent manner. HC diet-induced severe fat deposition in the mesenteric arteries, which is characteristic of SHRSP, was also decreased by HL-004. The ACAT activity of the small intestine and liver was decreased by HL-004. In particular, liver ACAT activity was significantly low in SHRSP given 0.09% HL-004, compared to that of normal animals. These results suggest that HL-004 is a systemic ACAT inhibitor and that the ACAT inhibition in the intestine, liver, and aorta is involved in the hypolipidemic and antiatherosclerotic effects of HL-004.

Acetanilides↗
PubMed1995

Effects of HL-004, a novel ACAT inhibitor, on cholesterol accumulation and removal in cultured smooth muscle cells from stroke-prone spontaneously hypertensive rats (SHRSP).

The cholesterol metabolism of cultured smooth muscle cells (SMC) from the thoracic aorta of SMC from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) was compared. SMC from SHRSP had a higher acylCoA:cholesterol acyltransferase (ACAT) activity and accumulated more cholesterol than those from WKY. By using SMC from SHRSP, the effects of a novel ACAT inhibitor, HL-004, on the accumulation and removal of cholesterol were investigated. HL-004 inhibited microsomal ACAT activity from rabbit liver, intestine, aorta, and cultured SMC of SHRSP with 50% inhibition (IC50) values of 2.2, 1.7, 7.9, and 20 nM, respectively. HL-004 suppressed the accumulation of the intracellular cholesteryl ester (CE), but did not affect the intracellular free cholesterol (FC) content. Removal of cholesterol from the lipid-loaded SMC was accelerated by HL-004. These effects of HL-004 on cholesterol levels showed a good parallel to ACAT inhibition. It would thus appear that the suppression of cholesterol accumulation and the removal of cholesterol in SMC by HL-004 can be attributed to its ACAT inhibition in the cell, which reduces the content of intracellular CE.

Acetanilides↗
PubMed1995

Demonstration of hereditarily accelerated proliferation in astrocytes derived from spontaneously hypertensive rats.

1. We examined the proliferative rates of cultured astrocytes isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant spontaneously hypertensive rats (SHRSR). Wistar-Kyoto rats (WKY) were used as a control for SHRSP and SHRSR. 2. In the presence of 10% fetal bovine serum (FBS), the doubling time for astrocytes from SHRSP and SHRSR was significantly shorter than WKY. 3. When quiescent astrocytes derived from SHRSP or SHRSR were released from serum-deprivation, the DNA synthesis was stimulated 13.3-fold and 12.5-fold, respectively, whereas only a 7.76-fold increase was observed in WKY astrocytes. 4. Further we studied the effects of two growth factors, epidermal growth factor (EGF) and fibroblast growth factor (FGF) on astrocytes proliferation. EGF induced greater DNA synthesis in SHRSP and SHRSR astrocytes compared with WKY astrocytes, although FGF had little or no effect. 5. Total cholesterol levels in SHRSP astrocytes and SHRSR astrocytes were significantly lower than that of WKY astrocytes, which was consistent with our previous observations in cultured vascular smooth muscle cells. 6. There was no difference in morphology among the cultured astrocytes from the three strains. 7. The abnormality of growth rate and cell membranes composition of astrocytes might be closely related to the genetic phenotypes (acute death of neurons and oedema of astrocytes) of SHRSP or SHRSR.

Animals↗
PubMed1995

A new locus on chromosome 3 strongly linked with salt-sensitive high blood pressure in female F2 from SHRSP and WKY rats.

1. We investigated candidate loci for salt-sensitive high blood pressure in F2 progeny from crossing Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. 2. The average systolic and diastolic blood pressure did not increase in male and female F2 progeny by the 12th day after salt loading. 3. In female F2 progeny, systolic and diastolic blood pressure became strongly linked with the MITR244 locus on chromosome 3, 1 month and 12 days after salt loading. 4. This locus became linked with blood pressure only in the female F2 progeny and not in the males. 5. These results indicate that hormonal factors and gender differences, in particular, might influence salt sensitivity.

Animals↗
PubMed1995

Intestinal calcium absorption and response of calcium regulating hormones in the stroke-prone spontaneously hypertensive rat as a model of osteoporosis.

1. Because of low levels of serum calcium (Ca) in stroke-prone spontaneously hypertensive rats (SHRSP), intestinal Ca absorption and urinary Ca excretion were examined. 2. SHRSP were observed to have lower intestinal Ca absorption and higher urinary Ca excretion, but with a latent function of intestinal Ca absorption able to respond with calcium regulating hormones to Ca loading in the aged, especially to a new Ca agent as examined in this study.

Animals↗
PubMed1995

Stroke-prone SHR and arteriolipidosis-prone SHR as models for atherosclerosis: their mechanisms and application for nutritional and pharmacological studies.

1. Peritoneal macrophages (Mphi) were harvested from non-stimulated 2 month old SHRSP and WKY, and incubated with acetyl LDL or [14C]-oleate-albumin complex to check total, free and esterified cholesterol (Cho) accumulation as well as acy coenzyme A-cholesterol acyltransferase (ACAT) activity and its activation by hyperlipidaemic serum. 2. Total and esterified Cho accumulation as well as ACAT activity were enhanced in Mphi from SHRSP compared with those from WKY. 3. To observe the dietary or pharmacological influence on atherogenesis, arteriolipidosis-prone SHR (ALR) were given a high fat cholesterol diet with 3% taurine or a Ca blocker (Nilvadipine, N; 30 mg/kg), both of which significantly decreased serum Cho level and clearly attenuated arterial fat deposition.

Animal Nutritional Physiological Phenomena↗
PubMed1995

Distinction of endothelial cell growth and fibrinolytic activity between WKY/Izm and SHRSP/Izm in vitro.

1. In the present study, endothelial cells (EC) growth and fibrinolytic activity of WKY/Izm and SHRSP/Izm were investigated in vitro. 2. EC were isolated from the thoracic aortas of WKY and SHRSP at the age of 8-9 weeks. Proliferative activities of EC were analysed with doubling time and DNA synthesis. Fibrinolytic activity was determined by tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) activities in cultured medium. 3. SHRSP-EC growth rate was significantly greater than WKY-EC growth rate in doubling time. In the assay for DNA synthesis, 5-bromo-2'-deoxy uridine incorporation rate in SHRSP-EC was significantly increased compared with that in WKY-EC. 4. The tPA activity in cultured medium of WKY-EC was 2-fold greater than that of SHRSP-EC, while PAI-1 activities were nearly equal in them. 5. These physiological distinctions of EC of SHRSP/Izm from that of WKY/Izm with close genetic background could be contributory genetic factors to hypertension-related vascular diseases in SHRSP.

Animals↗
PubMed1995

HMG-CoA reductase inhibitor affects blood pressure and vascular reactivity.

1. To investigate the effect of endogenous cholesterol synthesis on blood pressure and vascular response, a HMG CoA reductase inhibitor, pravastatin (1 or 10 mg/kg) was administered orally for 2 or 4 weeks to 8-13 week old spontaneously hypertensive rats (SHR/Izm) and normotensive Wistar-Kyoto (WKY/Izm) rats. 2. Blood pressure was significantly increased in the pravastatin-treated groups of both strains, but the elevation was observed in WKY after a longer treatment than in SHR. 3. After the thoracic aorta from 10-12 week old SHR and WKY was pretreated with pravastatin (10(-4) mol/L), the vascular response to norepinephrine was increased in pravastatin-treated SHR aorta but not in the WKY aorta in both contractivity and sensitivity. 4. These experiments suggest that the vascular response is affected by intracellular cholesterol synthesis pathway.

Animals↗
PubMed1995

Effect of lovastatin and fluoromevalonate on phosphatidylinositol 3-kinase activity stimulated with PDGF.

1. Phosphatidylinositol 3-kinase (PI3K) appears to have a crucial role in cellular proliferation induced by platelet-derived growth factor (PDGF). However, the mode of activation of the enzyme has been unclear so far. In the present study, we investigated the effects of a cholesterol lowering drug on [3H]-thymidine ([3H]-TdR) incorporation and PI3K activity in cultured vascular smooth muscle cells (VSMC) stimulated with PDGF. 2. PDGF stimulated both [3H]-TdR incorporation and PI3K activity immunoprecipitated with antiphosphotyrosine antibody in a dose dependent manner (ED50 was 4 ng/mL for [3H]-TdR uptake and 3 ng/mL for PI3K activity). Lovastatin inhibited serum-stimulated [3H]-TdR incorporation dose dependently. PI3K activity induced by PDGF was also inhibited in a dose dependent manner; however, its activity was 61% at 10(-6) mol/L, 72% at 10(-5) mol/L and 8% at 10(-4) mol/L of the control value. 3. These inhibitory effects of lovastatin were completely abolished by adding 1 mmol/L mevalonic acid (MVA), suggesting that MVA metabolites had some important role on the PI3K activation and cellular proliferation. 4. Fluoromevalonate (Fmev), a competitive inhibitor of mevalonate diphosphate (MVA-PP) decarboxylase, inhibited [3H]-TdR incorporation at concentrations more than 10(-6) mol/L. Moreover, marked inhibitory effect was observed at concentrations of 10(-7) and 10(-8) mol/L (76% of control). PI3K activity was also reduced by 10(-3) mol/L Fmev (0.2% of control). However, in contrast to [3H]-TdR uptake, there was no inhibitory effect detected at concentrations up to 10(-4) mol/L. 5. These results suggest that PDGF-stimulated PI3K activity as well as cellular proliferation was modified by protein isoprenylation.

Animals↗
PubMed1995

[Repetitive discharges of proximal origin in a patient with carcinomatous sensory neuropathy].

Repetitive discharges of a motor unit potential were observed during ulnar nerve conduction studies in a patient with pathologically verified carcinomatous sensory neuropathy. The repetitive discharges in this patient had a latency similar to that of the F-wave latency. The first discharge was followed by discharges identical in configuration every 3 to 4 msec. These discharges responded to all of the suprathreshold stimuli, had a constant configuration, and exhibited jitter in their latency. When paired stimuli were applied, the second stimulus collided with the first discharge, leaving the afterdischarges behind at the previous position. Based on these electromyographic findings, the origin of these repetitive discharges is believed to have been the proximal part of a motor axon or a neighboring demyelinating lesion, since degenerative changes have been demonstrated in ventral roots as well as dorsal root ganglia in this disease.

Action Potentials↗