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T Miyauchi

Publications and source records attributed to T Miyauchi.

At least 19 recordsLinked to original sources
PubMed2000

Effects of para-nonylphenol on 92 kDa gelatinase secretion by human peripheral lymphocytes and U937 cells in vitro.

Much attention has focused on environmental estrogenic chemicals such as para-nonylphenol which disrupt various tissues via the estrogen receptor. We studied effects of para-nonylphenol on gelatinase secretion by human lymphocytes in vitro. para-Nonylphenol (0.05-50 microM) dose dependently suppressed 92 kDa gelatinase secretion. The suppressive effect of 25 and 50 microM para-nonylphenol was completely blocked by tamoxifen. We also studied the effects of para-nonylphenol (0.05-50 microM) on 92 kDa gelatinase secretion by human leukemia U937 cells. para-Nonylphenol suppressed 92 kDa gelatinase secretion in a dose-dependent manner. The suppressive effect of 50 microM para-nonylphenol was completely blocked by tamoxifen. Estradiol did not significantly suppress 92 kDa gelatinase secretion. Our results suggest that para-nonylphenol suppressed 92 kDa gelatinase secretion via the estrogen receptor, however, para-nonylphenol interacts with the estrogen receptor in a manner distinct from estradiol. As this assay system is simple and rapid, it may prove useful to evaluate toxic effects of para-nonylphenol on human blood cells.

Estradiol↗
PubMed2000

Chronic treatment with probucol effectively inhibits progression of pulmonary hypertension in rats.

It has been reported that probucol is a lipid-lowering agent having a strong antioxidative effect and inhibitory action on vascular smooth muscle cell proliferation. In this work, we studied the effect of treatment with a 1% probucol diet on pulmonary hypertension induced by monocrotaline (MCT) in rats. Rats were fed a control or 1% probucol-supplemented diet for 7 days, then given a single subcutaneous injection of 60 mg/kg MCT or saline, and continuously fed the same diet for 20 days, respectively. MCT caused an increase in right ventricular systolic pressure (RVSP), an indicator of pulmonary hypertension, and central venous pressure (CVP) on day 20. In rats receiving a diet containing 1% probucol, RVSP was significantly lower than that in rats treated with control diet, and CVP remained essentially at the basal level. On day 20, MCT also caused an increase in the ratio of right ventricular (RV) to body weight (BW), compared to the control value, indicating the development of RV hypertrophy in MCT rats. RV hypertrophy was significantly inhibited in 1% probucol-treated rats. These findings suggest that chronic treatment with probucol effectively inhibits the progression of pulmonary hypertension in rats.

Animals↗
PubMed2000

Long-term endothelin receptor antagonist administration improves alterations in expression of various cardiac genes in failing myocardium of rats with heart failure.

BACKGROUND: We reported that long-term (3-month) treatment with the endothelin (ET) type A (ET(A)) receptor antagonist BQ-123 markedly improved survival in rats with chronic heart failure (CHF). However, it is not known whether long-term treatment with an ET receptor antagonist improves alterations in the expression of cardiac genes in failing hearts. METHODS AND RESULTS: CHF rats and control sham-operated rats were treated with BQ-123, SB209670 (ET(A/B) dual receptor antagonist), or saline (vehicle) for 3 months. The survival of CHF rats was markedly higher in the BQ-123 or SB209670 treatment group than in the saline treatment group. The changes in the gene expression of classic molecular markers for failing hearts (mRNA levels of atrial natriuretic peptide and beta-myosin heavy chain) were greatly inhibited by BQ-123 or SB209670 treatment in CHF rats. Long-term BQ-123 treatment also normalized the alterations in the expression of functional molecular markers in failing hearts (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1). CONCLUSIONS: We demonstrated for the first time that long-term (3-month) treatment with an ET receptor antagonist improves the alterations in the expression of various cardiac genes of classic molecular markers (eg, mRNA in atrial natriuretic peptide and beta-myosin heavy chain) and of functional molecular markers (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1) in the failing hearts of CHF rats, suggesting that the great improvement of survival in CHF rats by an ET blocker is partly attributed to the prevention of molecular changes in failing hearts.

Animals↗
PubMed2000

Decreased serum concentrations of nitric oxide metabolites among Chinese in an endemic area of chronic arsenic poisoning in inner Mongolia.

Prolonged exposure to arsenic results in peripheral and cardiovascular manifestations, as does impaired production of endothelial nitric oxide (NO). In vitro studies have indicated that endothelial cells undergo damage by arsenic. However, no information has been available on the relationship between NO synthesis and chronic arsenic poisoning in humans. The present study was designed to reveal this question. The subjects were 33 habitants who continued to drink well water containing high concentrations of inorganic arsenic (mean value = 0.41 microg/ml) for about 18 years in Inner Mongolia, China, and 10 other people who lived in this area but exposed to minimal concentrations of arsenic (mean value = 0.02 microg/ml) were employed as controls. Mean blood concentration of total arsenic was six times higher in exposed subjects than controls; 42.1 vs. 7.3 ng/ml, p <.001. Mean serum concentration of nitrite/nitrate, stable metabolites of endogenous NO, was lower in arsenic-exposed subjects than in controls: 24.7 vs. 51.6 microM, p<.001. In total samples, an inverse correlation with serum nitrite/nitrate levels was strong for blood inorganic arsenic (r = -0.52, p <.001) and less strong for its metabolites, monomethyl arsenic (r = -0.45, p<.005) and dimethyl arsenic (r = -0.37, p<.05). Furthermore, serum nitrite/nitrate concentration was significantly correlated with nonprotein sulfhydryl level in whole blood (r = 0.58, p<.001). In an in vitro study, we demonstrated that inorganic arsenite or arsenate suppresses the activity of endothelial NO synthase in human umbilical vein endothelial cells. These results suggest that long-term exposure to arsenic by drinking well water possibly reduces NO production in endothelial cells, resulting in a decrease in reduced nitrite/nitrate concentrations. Peripheral vascular disorders caused by arsenic may be attributable in part to impairment of NO production in vivo.

Adolescent↗
PubMed2000

Corresponding distributions of increased endothelin-B receptor expression and increased endothelin-1 expression in the aorta of apolipoprotein E-deficient mice with advanced atherosclerosis.

Endothelin (ET)-1 causes proliferation of vascular smooth muscle cells (VSMC). Although it has been reported that stimulation of ET(B) receptors as well as ET(A) receptors promote proliferation of VSMC, the precise distribution of each receptor subtype in atherosclerotic vessels is unknown. Previous studies demonstrated that apolipoprotein E (apoE)-deficient mice have hypercholesterolaemia and develop severe atherosclerosis. To investigate the pathophysiological roles of vascular ET system in atherosclerosis, we examined preproET-1 messenger ribonucleic acid expression in the aorta of apoE-deficient mice, and performed immunohistochemical staining for ET-1 and each ET receptor subtype (ET(A) and ET(B) receptors) in the atherosclerotic lesions of these mice. The level of preproET-1 mRNA in the aorta was significantly higher in the apoE-deficient mice than in the control mice. Strong ET-1 staining was observed in the macrophage-foam cells, intimal and medial VSMC in the atherosclerotic lesions of the apoE-deficient mice. In addition, in the atherosclerotic lesions, strong ET(B) receptor staining was observed in the macrophage-foam cells, intimal and medial VSMC, which distribution corresponded closely to that of ET-1. ET(A) receptor staining was observed in the medial VSMC of both groups, but not in the macrophage-foam cells of the apoE-deficient mice. ET(A) receptor staining in the medial VSMC was stronger in the apoE-deficient mice than in the control mice. These results suggest that the vascular ET system, including ET-1 and ET receptors, is activated in the atherosclerotic lesions of apoE-deficient mice. Since the distribution of strong ET(B) receptor staining corresponded closely to that of ET-1, it is suggested that the ET system, mediated by ET(B) receptors, has an important role in the pathophysiology of the atherosclerotic lesions of apoE-deficient mice.

Animals↗
PubMed2000

Hypotensive effect of endothelin-1 via endothelin-B-receptor pathway on pulmonary circulation is enhanced in rats with pulmonary hypertension.

The pharmacological characterization of endothelin-1 (ET-1) in the pulmonary circulation in pulmonary hypertension (PH) is not known precisely. We investigated the effect of intravenous injection of ET-1 (1000 pmol/kg) on right ventricular systolic pressure (RVSP) (which is equal to systolic pulmonary arterial pressure) in rats with monocrotaline-induced PH. ET-1 decreased RVSP in PH rats; however, ET-1 did not alter RVSP in control rats, suggesting that ET-1 causes dilatation of the pulmonary artery in PH rats. Under pretreatment with the endothelin-A- (ET(A)) receptor antagonist BMS 193884, ET-1 decreased RVSP in PH rats more than in control rats, suggesting that pulmonary vasodilator action of ET-I mediated via the ET(B)-receptor pathway is augmented in PH rats. Under pretreatment with the ET(A/B)-receptor antagonist SB 209670, the effect of ET-1 in lowering pulmonary arterial pressure was abolished in both groups of rats. These results suggest that the hypotensive effect of ET-1 on pulmonary circulation mediated via the ET(B)-receptor pathway is enhanced in PH rats compared with control normal rats. It is considered that the blockade of only the ET(A)-receptor pathway is preferable to the blockade of both the ET(A)- and ET(B)-receptor pathways in the treatment of PH.

Animals↗
PubMed2000

Impairment of cardiac energy metabolism in vivo causes hemodynamic abnormality and increases cardiac expression of preproendothelin-1 mRNA.

We investigated whether impairment of myocardial energy metabolism attenuates cardiac function and increases cardiac endothelin-1 (ET-1) gene expression in rats. Three weeks after commencing administration of cobalt chloride (CoCl2), an inhibitor of mitochondrial function, the peak positive first derivative of left ventricular (LV) pressure, an indicator of myocardial contractility, was significantly decreased in the CoCl2-treated rats. LV end-diastolic pressure and right ventricular systolic pressure were increased in the CoCl2-treated rats. Echocardiography showed that fractional shortening was significantly decreased in the CoCl2-treated rats. Myocardial expressions of acyl-CoA synthase mRNA, an enzyme involved in fatty acid utilization, was markedly decreased in the CoCl2-treated rats. Under such conditions, myocardial expression of preproendothelin-1 mRNA and atrial natriuretic peptide (ANP) mRNA, molecular markers of heart failure, was markedly increased in the CoCl2 rats. In conclusion, the data suggest that impairment of myocardial energy metabolism causes hemodynamic abnormality and increases molecular markers of heart failure (ET-1, ANP mRNA). These data suggest that myocardial energy metabolism is one of the factors involved in the upregulation of ET-1 gene expression in the failing heart.

Animals↗
PubMed2000

Mitochondrial dysfunction of cardiomyocytes causing impairment of cellular energy metabolism induces apoptosis, and concomitant increase in cardiac endothelin-1 expression.

It has been reported that at the end stage, apoptosis is involved in the progression of heart failure. It is suggested that cardiac energy metabolism is impaired during the progression of heart failure. Although the mechanism of induction of apoptosis in the failing heart varies according to the model of heart failure, it is not known whether an impairment of energy metabolism in cardiomyocytes is a primary cause of apoptosis. In this study, we applied mitochondrial inhibitors, such as rotenone, cobalt chloride and antimycin A, which inhibit mitochondrial function at different sites of the mitochondrial respiratory chain, to cardiomyocytes. All these reagents markedly decreased 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT) reduction activity, an indicator of mitochondrial function, of cardiomyocytes and greatly increased glucose consumption, suggesting that cardiac energy metabolism is switched from beta-oxidation of fatty acid to glycolysis. It was shown that after 48-72 h of treatment with each reagent, apoptosis was shown to occur by DNA laddering and increase in caspase activity. Interestingly, each reagent with a different action site greatly activated caspase-3, but not caspase-8 activity, suggesting that mitochondria are involved in induction of apoptosis. On the other hand, within 24 h of the treatment, when apoptosis of cardiomyocytes was not observed, the treated cardiomyocytes showed a marked increase in preproendothelin-1 and atrial natriuretic peptide (ANP) gene expressions. In conclusion, the present study suggests that mitochondrial dysfunction with impaired energy metabolism elevates gene expression of cardiac ET-1, an aggravating factor in heart failure, and then finally induces apoptosis in cardiomyocytes. The finding of marked increases in expression of molecular markers (ET-1 mRNA and ANP mRNA) in the failing heart, followed by apoptosis in the treated cardiomyocytes suggests that the inhibition of mitochondrial function of cultured cardiomyocytes provides a possible new in vitro model of heart failure.

Animals↗
PubMed2000

Mitochondrial dysfunction increases expression of endothelin-1 and induces apoptosis through caspase-3 activation in rat cardiomyocytes in vitro.

We have reported that the expression of endothelin-1 (ET-1) increases in the failing heart. With the progress of heart failure, it has been reported that energy metabolism switches from mitochondrial b-oxidation to glycolysis. Furthermore, it has been reported that apoptosis is induced in the failing heart. However, it is not known how the gene expression of preproendothelin-1 and cellular apoptosis are affected by the mitochondrial dysfunction. Therefore, in order to elucidate this problem, we developed an in vitro model of mitochondrial dysfunction using rotenone, a mitochondrial respiratory chain complex I inhibitor, and studied preproendothelin-1 gene expression and apoptosis. Rotenone greatly increased the gene expression of pre-proendothelin-1 in cardiomyocytes. This result suggests that the gene expression of preproendothelin-1 is induced by the mitochondrial dysfunction. Furthermore, treatment of cardiomyocytes with rotenone induced an elevation of caspase-3 activity, and caused a marked increase in DNA laddering, an indication of apoptosis. In conclusion, it is suggested that mitochondrial impairment in primary cultured cardiomyocytes induced by rotenone in vitro, mimics some of the pathophysiological features of heart failure in vivo, and that ET-1 may have a role in myocardial dysfunction with impairment of mitochondria in the failing heart.

Animals↗
PubMed2000

Endothelin-A-receptor antagonist and oral prostacyclin analog are comparably effective in ameliorating pulmonary hypertension and right ventricular hypertrophy in rats.

Pulmonary hypertension (PH) has a poor prognosis and is a drug-resistant disease. Recently, it has been reported that continuous intravenous prostacyclin (PGI2) administration is effective for PH. In this study, we compared the effects of chronic treatment with an endothelin-A- (ETA) receptor antagonist with an oral PGI2 analog on PH in rats. We administered the ETA-receptor antagonist TA-0201 or beraprost sodium (BPS), which is an orally active PGI2 analog, to monocrotaline- (MCT) induced PH rats. Each drug was given orally for 19 days. The rats were divided into the following four groups: (1) normal rats with vehicle (control); (2) PH rats with vehicle treatment (PH + vehicle); (3) PH rats with TA-0201 treatment (0.5 mg/kg/day) (PH + TA-0201); (4) PH rats with BPS treatment (100 microg/kg/day) (PH + BPS). Nineteen days after MCT injection, Pp/Ps [the ratio of right ventricular (RV) systolic pressure to systemic systolic blood pressure) and the ratio of the RV weight to the body weight (RV/BW), indicators of PH and RV hypertrophy. were markedly higher in the PH + vehicle group than in the control (healthy) group. The increase in Pp/Ps and RV/BW was significantly depressed in the PH + TA-0201 group and PH + BPS group to a similar extent. The expression of beta-myosin heavy chain (MHC) mRNA, a molecular marker for cardiac hypertrophy, in the RV was greatly increased in the PH + vehicle group and this increase was inhibited in the PH + TA-0201 group and PH + BPS group to a similar effect. In conclusion, treatment with an ETA-receptor antagonist or an oral PGI2 analog is comparably effective in the prevention of progression of PH and RV hypertrophy.

Administration, Oral↗
PubMed2000

Endothelin-1 and right-sided heart failure in rats: effects of an endothelin receptor antagonist on the failing right ventricle.

The development of pulmonary hypertension (PH) causes right-sided heart failure. We investigated whether chronic treatment with the endothelin-A- (ETA) receptor antagonist BMS-193884 in rats with monocrotaline- (MCT) induced PH improves right-sided heart failure. Administration of BMS-193884 (100mg/kg) was commenced on the day before treatment with MCT. At 19 days, hemodynamics were measured under anesthesia and hearts were removed. The right ventricular systolic pressure (RVSP), an indicator for pulmonary hypertension, was remarkably elevated in the PH group compared with the normal control group. BMS-193884 effectively prevented this elevation. The central venous pressure, an indicator for right-sided heart failure, was markedly increased in the PH group. This increase was reduced to the normal level by BMS-193884. In the failing right ventricle of the PH group, the expression of atrial natriuretic peptide (ANP) mRNA, which is a molecular marker for the failing heart, was markedly increased. BMS-193884 greatly prevented this increase. The present study suggests that ET-1 contributes to the right-sided heart failure caused by PH and that an ETA-receptor antagonist is a beneficial drug which improves both hemodynamics and cardiac gene expression in the failing right ventricle.

Animals↗
PubMed2000

Antihypertensive effects of a mixed endothelin-A- and -B-receptor antagonist, J-104132, were augmented in the presence of an AT1 -receptor antagonist, MK-954.

The single oral administration of a mixed endothelin-A-and -B- (ETA/ETB) receptor antagonist, J-104132 (L-753,037) decreased the blood pressure in conscious spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and Dahl salt-sensitive hypertensive rats fed high-salt diet (DS-H) at doses of 3 and 10 mg/kg, with a duration of approximately 24 h. The magnitude of the antihypertensive effects was greater in DS-H than in SHR and SHRSP Preproendothelin-1 mRNA expression in the kidney and aorta was greater (about twofold) in DS-H than that in nonnotensive Dahl salt-resistant rats fed high-salt diet (DR-H), while there was no difference in preproendothelin-1 mRNA expression between SHR and Wistar Kyoto rats (WKY). An AT1-receptor antagonist, MK-954 (Losartan), also attenuated hypertension in SHR and SHRSP at oral doses of 3 and 10 mg/kg, but bad no effect in DS-H. The concomitant treatment with MK-954 and J-104132 showed additive antihypertensive effects in SHR and SHRSP. In DS-H, MK-954 potentiated the antihypertensive effects of J-104132. From these results, we suggest that: (1) the contribution of endothelin (ET) to the maintenance of hypertension is greater in salt-sensitive hypertensive models than in SHR and SHRSP; (2) the antihypertensive efficacy of ETA/ETB blockade is augmented by AT1-receptor blockade; (3) ET blockers alone or in combination with AT1 antagonists could be useful in the treatment of hypertension for patients who do not respond adequately to renin-angiotensin system inhibitors alone.

Angiotensin Receptor Antagonists↗
PubMed2000

Kink-breather solution in the weakly discrete Frenkel-Kontorova model

The discrete Frenkel-Kontorova model, having the sine-Gordon equation as the continuous analog, was investigated numerically at a small degree of discreteness. Interaction between a kink and a breather in a discrete system was compared with the exact three-soliton solution to the continuous sine-Gordon equation. Nontrivial effects of discreteness were found numerically. One is that a kink and a breather in the discrete system are mutually attractive quasiparticles, so they can be regarded as a three-soliton oscillatory system. The other is the energy exchange between a kink and a breather when their collision takes place in a vicinity of a separatrix solution to the continuous sine-Gordon equation. We have estimated numerically the kink-breather binding energy EB and the maximum possible exchange energy EE for different breather frequencies omega. The results suggest that there is a threshold breather frequency for the "spontaneous" breaking up of the three-soliton oscillatory system into a kink and a breather moving in opposite directions.

Journal Article↗
PubMed2000

Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts.

Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense exercise on the expression of NO synthase (NOS) and the tissue level of nitrite (NO(2)(-))/nitrate (NO(3)(-)) (i.e., NOx), which are stable end products of NO in the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise, the heart was quickly removed. Control rats remained at rest during the same 45-min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly lower in the exercised rats than in the control rats. Western blot analysis confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx level in the heart was significantly lower in the exercised rats than in the control rats. The present study revealed for the first time that production of NO in the heart is decreased by intense exercise. Because NO attenuates positive inotropic and chronotropic responses to beta(1)-adrenergic stimulation in the heart, the decrease in cardiac production of NO by intense exercise may contribute to the acceleration of increase in myocardial contractility and heart rate during intense exercise.

Animals↗
PubMed2000

[An elderly case of ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade].

We reported a case of successful aortic arch replacement using selective cerebral perfusion for ruptured distal aortic arch aneurysm (DAAA) with cardiac tamponade. A 80-year-old man who had preoperative episode of severe chest pain. Computed tomography showed saccular DAAA and pericardial effusion. He was diagnosed as ruptured DAAA with hemorrhagic cardiac tamponade. We performed urgent graft replacement of the aortic arch using selective cerebral perfusion. Postoperatively he had no complication. Thirty days after the operation he was discharged from the hospital and he is now leading a normal life.

Aged↗