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Biomedical subjects

T Ogihara

Publications and source records attributed to T Ogihara.

At least 505 records · Page 28Linked to original sources
PubMed1994

Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters.

We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.

Angiotensin II↗
PubMed1994

Effects of age and hypertension on autonomic nervous regulation during passive head-up tilt.

To study the effects of age and hypertension on autonomic nervous function with passive postural change, we examined 31 normotensive subjects (25 to 85 years old) and 31 hypertensive patients (21 to 71 years old) without any cardiac disease, diabetes mellitus, or neurological disorders. Subjects were passively placed in a 60 degrees head-up tilting position after 15 minutes in the supine position. Autonomic nervous function was evaluated by frequency domain analysis of heart rate with the autoregressive method. Using low-frequency (0.1 Hz) and high-frequency (0.25 Hz) peaks, the ratio of low- to high-frequency power (L/H) was calculated as an index of sympathetic activity and the ratio of high to total power (%HF) as that of parasympathetic activity. With the patient in the supine position, total power spectral density declined logarithmically with age in normotensive subjects and hypertensive patients, but %HF and L/H showed no changes. In response to passive tilting, L/H was increased and %HF was decreased in the normotensive subjects, and these responses declined with age logarithmically. In contrast, hypertensive patients exhibited less autonomic response to postural change regardless of age. These results suggest that autonomic neural response to tilt is decreased with age; however, attenuation of the response by hypertension is not associated with an increase in age.

Adult↗
PubMed1994

Role of glucose intolerance in cardiac diastolic function in essential hypertension.

Insulin resistance and glucose intolerance have been suggested to be involved in the pathogenesis of various cardiovascular diseases. We examined the role of glucose intolerance in cardiac performance and cardiac hypertrophy in 33 patients with essential hypertension (28 to 71 years of age, mean +/- SD: 53 +/- 13 years) who had never been treated. Patients with obesity (body mass index > 30 kg/m2) or overt diabetes were excluded. Plasma glucose and insulin were measured after oral administration of 75 g glucose. The incremental areas of glucose and insulin were used as indices of glucose intolerance and insulin resistance, respectively. Patients with impaired glucose tolerance according to World Health Organization criteria (n = 12) showed a significantly higher ratio of peak velocity during atrial contraction to early left ventricular filling phase (A/E ratio) than those with normal glucose tolerance (n = 21) despite similar age, blood pressure, and left ventricular mass index. By regression analysis, left ventricular mass index positively correlated with systolic blood pressure (r = .392, P < .05) but not with any parameters of glucose and insulin metabolism. A/E ratio determined by a Doppler system significantly correlated with age ( r = .776) and fasting and peak levels and incremental area of plasma glucose (r = .529, r = .468, and r = .634) but not with those parameters of insulin. In contrast, ejection fraction was not related to blood pressure, glucose tolerance, or insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Endothelin-1 in cerebrospinal fluid in elderly patients with hypertension and dementia.

Endothelin-1, a potent endothelium-derived vasoconstrictive peptide, is also known to exist in the central nervous system. We determined endothelin-1-like immunoreactivity in cerebrospinal fluid by a radioimmunoassay in 32 normotensive or hypertensive elderly subjects (79 +/- 8 years old) with or without multi-infarction dementia. The mean value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) elevated in subjects with essential hypertension (> or = 160/95 mm Hg, n = 5, 79 +/- 9 years old) compared with those with borderline hypertension (140-159/90-94 mm Hg, n = 4, 78 +/- 5 years old) and normotensive subjects (< 140/90 mm Hg, n = 23, 79 +/- 8 years old). The value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) positively correlated with both systolic (r = .38) and diastolic (r = .42) blood pressures in all subjects. On the other hand, mean values of endothelin-1-like immunoreactivity in cerebrospinal fluid were also significantly (P < .05) elevated in the groups of patients with multi-infarction dementia that had profoundly decreased Mini-Mental State scores (< or = 10, n = 6) and moderately decreased Mini-Mental State scores (11 to 20, n = 14) compared with those values in subjects with normal cognitive function (score for Mini-Mental State > or = 21, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Intimal hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides.

The cell cycle regulatory enzyme, cdk (cyclin-dependent kinase) 2 kinase, is activated in the rat carotid artery after balloon angioplasty injury, and may mediate smooth muscle proliferation. To test the hypothesis that inhibition of the expression of this key enzyme can inhibit intimal hyperplasia, we studied the effect of antisense phosphorothioate oligodeoxynucleotides (ODN) against cdk 2 kinase administered by intraluminal delivery using hemagglutinating virus of Japan (HVJ)-liposome-mediated transfer. The specificity of antisense cdk 2 ODN was confirmed by the observation that mRNA level of cdk 2 kinase in injured vessels was markedly diminished by the antisense ODN treatment. At 2 wk after transfection, antisense cdk 2 ODN treatment (15 microM) resulted in a significant inhibition (60%) in neointima formation, compared with sense ODN-treated and untreated vessels. Since we have previously observed that cell division cycle 2 kinase mRNA was also activated after vascular injury, we administered the combination of antisense cdc 2 and cdk 2 ODN in this study. Antisense cdc 2 ODN alone (15 microM) only reduced intimal formation by 40%. Combined antisense treatment resulted in near complete inhibition of neointima formation. To understand the mechanism of the sustained effect of a single antisense ODN administration, we examined kinetics of ODN in the vessel wall. Using phosphorothioate FITC-labeled ODN, we transfected carotid artery using the HVJ-liposome method. Fluorescence localized immediately to the medial layer, and persisted up to 2 wk after transfection. These results demonstrate that a single intraluminal administration of antisense ODN directed to cell cycle regulatory genes (e.g., cdk 2 kinase) using the HVJ method can result in a sustained inhibition of neointima formation after balloon angioplasty in rat carotid injury model.

Angioplasty, Balloon↗
PubMed1994

Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth.

In addition to the atria, recent evidence suggests that atrial natriuretic peptide (ANP) is also synthesized in other tissues. Of particular interest is the location of ANP mRNA in the vessel wall. We and others have shown that exogenously added ANP inhibited the growth of endothelial cells and vascular smooth muscle cells (VSMC) in culture. However, it is not known if the locally synthesized ANP would act similarly. Because cultured endothelial cells and VSMC have lost the ability to express the endogenous ANP gene, we have transfected cells in culture with an expression vector expressing rat ANP and have examined the effects on growth. Cultured endothelial cells transfected with an ANP expression vector synthesized and secreted high levels of ANP. These cells also showed significantly lower rates of DNA synthesis under basal and fibroblast growth factor (FGF)-stimulated conditions. Addition of conditioned medium from endothelial cells transfected with ANP vector to nontransfected endothelial cells resulted in the significant increase in cyclic GMP. Similarly, conditioned media collected from endothelial cells transfected with ANP vector also decreased DNA synthesis in VSMC. Coculture of ANP-transfected endothelial cells with quiescent VSMC showed that released ANP from endothelial cells inhibited DNA synthesis in VSMC. Finally, we examined the autocrine effect of direct transfection of ANP vector into VSMC. Transfection of the ANP vector decreased DNA synthesis in VSMC under basal and angiotensin II-stimulated conditions. Similarly, transfection of the ANP vector resulted in a decrease in the PDGF and serum (5%)-stimulated DNA synthesis of VSMC. These results demonstrate that endogenously produced ANP can exert autocrine and paracrine inhibitory effects on endothelial cell and VSMC growth. In vivo gene transfer of ANP may provide us with the opportunity of gene therapy for vascular diseases in which the abnormalities are vasoconstriction and pathological growth.

Animals↗
PubMed1994

Evidence for direct local effect of angiotensin in vascular hypertrophy. In vivo gene transfer of angiotensin converting enzyme.

In vitro studies have demonstrated that angiotensin (Ang) II directly stimulates vascular smooth muscle cell (VSMC) growth. However, it is still unclear if Ang II exerts a direct effect on vascular hypertrophy in vivo independent of its effect on blood pressure. In vivo gene transfer provides the opportunity to assess the effects of increased activity of the vascular angiotensin system in the intact animal while avoiding an increase in circulating angiotensin or in blood pressure. Accordingly, we transfected the human angiotensin converting enzyme (ACE) vector into intact rat carotid arteries by the hemagglutinating virus of Japan-liposome method. 3 d after transfection, we detected increased ACE activity in the transfected artery. Immunohistochemistry localized immunoreactive ACE in the medial VSMC as well as in the intimal endothelial cells. The increase in vascular ACE activity was associated with a parallel increase in DNA synthesis as assessed by BrdU (bromo-deoxyuridine) index and vascular DNA content. This increase in DNA synthesis was abolished by the in vivo administration of an Ang II receptor-specific antagonist (DuP 753). Morphometry at 2 wk after transfection revealed an increase in the wall to lumen ratio of the ACE-transfected blood vessel as compared with control vector transfected vessels. This was accompanied by increases in protein and DNA contents without an increase in cell number. Local transfection of ACE vector did not result in systemic effects such as increased blood pressure, heart rate, or serum ACE activity. These morphological changes were abolished by the administration of the Ang II receptor antagonist. In this study, we used in vivo gene transfer to increase local expression of vascular angiotensin converting enzyme and provided proof that increased autocrine/paracrine angiotensin can directly cause vascular hypertrophy independent of systemic factors and hemodynamic effects. This approach has important potentials for defining the role of autocrine/paracrine substances in vascular biology and hypertension.

Angiotensin I↗
PubMed1994

Protective effect of cisapride against indomethacin-induced obstruction of the gastric mucosal hemodynamics in rats.

We investigated the effect of cisapride, a gastroprokinetic agent, on the obstructed gastric mucosal hemodynamics induced by indomethacin using an organ reflectance spectrophotometry system in rats. Indomethacin (10 mg/kg, i.v.) reduced both the gastric mucosal blood volume and the gastric mucosal blood oxygenation. Pretreatment with cisapride (0.1 mg/kg, i.v.) prevented these deteriorations. The presently-clarified gastric mucosal protective effect of cisapride may contribute to its therapeutic efficacy.

Animals↗
PubMed1994

Increased release of platelet-derived growth factor from platelets in chronic liver disease.

The concentrations of platelet-derived growth factor in serum in 7 healthy controls (61 +/- 9 years; mean +/- SD) and 10 patients (62 +/- 8 years) with chronic liver disease (chronic hepatitis and/or liver cirrhosis) were compared. The plasma concentration of platelet-derived growth factor was below the detection limit (< 0.45 microgram/l) in all the subjects studied. The peripheral blood platelet count in patients with chronic liver disease was significantly lower than that in control subjects. However, the concentration of platelet-derived growth factor in serum, which was assumed to be released from platelet, was similar in patients with chronic liver disease and control subjects. These results indicate that the mean amount of platelet-derived growth factor released from the same number (10(9)) of platelets, calculated from the serum platelet-derived growth factor concentration and the peripheral blood platelet count, in patients with chronic liver disease (33 +/- 11 ng/10(9) platelets) was significantly (p < 0.01) higher than that in control subjects (14 +/- 5 ng/10(9) platelets). Moreover, the amount of platelet-derived growth factor released from 10(9) platelets inversely correlated with the serum concentration of pseudocholinesterase activity (r = -0.65, p < 0.01), and correlated positively (r = 0.91, p < 0.01) with the percent retention of indocyanine green in serum, in all subjects studied. These findings suggest that the amount of platelet-derived growth factor releasable from platelets of patients with chronic liver disease is higher than that in normal subjects and that it correlates with the severity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Partial DiGeorge syndrome at the age of thirty-four.

A 34-year-old man with partial DiGeorge syndrome suffered from seizures and mental retardation from the age of three years. He was diagnosed as having primary hypoparathyroidism by the Ellsworth-Howard test at the age of 22. He was also found to have a right aortic arch. Immunological studies revealed the presence of immature T cells (CD 38+, OKT 9+), although the subsets and function of his T cells were almost normal. The facts that the cardiovascular anomaly and immunodeficiency were mild and the hypoparathyroidism was well controlled, may account for his survival to this age.

Adult↗
PubMed1994

Differential regulation of brain angiotensin II in genetically hypertensive and normotensive rats after nephrectomy.

To investigate the role of tissue angiotensin II (Ang II) in the maintenance of hypertension after nephrectomy in spontaneously hypertensive rats (SHR), Ang II levels were measured in various tissues of both 12-week-old SHR and normotensive control, Wistar-Kyoto rats (WKY), 48 h after nephrectomy or sham operation. Ang II was determined by radioimmunoassay coupled with high performance liquid chromatography. Nephrectomy caused a decrease of plasma renin activity and plasma Ang II concentration in both SHR and WKY. Aortic Ang II levels were significantly lowered by nephrectomy only in WKY, and not in SHR. Ang II levels in hypothalamic block, brainstem and cerebellum of SHR increased after nephrectomy, whereas those of WKY were unchanged. Intracerebroventricular administration of ceronapril, an angiotensin converting enzyme inhibitor, significantly decreased sustained high blood pressure in SHR 48 h after nephrectomy compared with vehicle administration, whereas intravenous administration had no effect. These results suggest that in spite of the important role of the renal renin-angiotensin system in maintenance of high blood pressure in SHR, control mechanisms may switch to other systems after nephrectomy, and that the increased brain Ang II levels after nephrectomy may be related to these mechanisms.

Angiotensin II↗
PubMed1994

Homocysteine induces iron-catalyzed lipid peroxidation of low-density lipoprotein that is prevented by alpha-tocopherol.

Homocystinuria is an inborn error of methionine metabolism that is characterized by the premature development of arteriosclerosis. As one of the major factors in the pathogenesis of arteriosclerosis, modification of low-density lipoprotein (LDL) has received widespread attention by many investigators. In this study, to elucidate the relationship between elevated homocysteine levels and premature arteriosclerosis, we investigated the role of homocysteine in the iron-catalyzed oxidative modification of LDL. When LDL isolated from a healthy subject was incubated with homocysteine and ferric ion, a gradual decrease of polyunsaturated fatty acids (PUFA), formation of thiobarbituric acid-reactive substances (TBARS) and fluorescent substances, and the fragmentation of apoprotein B (apoB) were observed. The extent of oxidative modification was dependent on the concentration of homocysteine. Modification of LDL was suppressed until the remaining alpha-tocopherol concentration reached a critical level. When the alpha-tocopherol content of LDL was increased by 2.6-fold, both the formation of TBARS and the fragmentation of apoB were suppressed. These results suggest that homocysteine might promote iron-catalyzed oxidation of LDL and imply its role for the development of premature arteriosclerosis.

Adult↗
PubMed1994

[Risk factors related to the wall thickness of carotid artery assessed by ultrasonography].

Progression of atherosclerotic lesion of the carotid artery is suggested to induce the development of cerebrovascular events. We evaluate the risk factors related to carotid artery, wall thickness by ultrasonography. A total of 159 patients, who had received no medication for hypertension or hyperlipidemia were enrolled in this study. The wall thickness of carotid artery was evaluated as an intima-media (IM) complex measured by B-mode ultrasonography with a 7.5 MHz probe. Simple regression analysis demonstrated significant correlation between the IM complex and both age and systolic blood pressure, but not with fasting levels of plasma glucose, hemoglobin A1c, total and HDL cholesterol, triglyceride or gender. Stepwise regression analysis showed age and systolic blood pressure contribute to IM thickness (r = 0.623). However, in patients aged 60 or over, blood pressure did not contribute to the IM wall thickness. Smoking was not a risk factor for IM thickness, but the Brinkman Index (daily consumption of cigarettes x years smoking) was significantly higher in patients with plaques in the carotid artery than those without it. These results suggest that high blood pressure is a risk factor for mild atherosclerotic lesions of the carotid artery for those aged under 60. Smoking may contribute to the formation of plaque, which may consequently lead to the ischemic cerebrovascular disease.

Aged↗
PubMed1994

[Effects of pravastatin administration for 12 months on serum lipid levels in aged patients with hypercholesterolemia].

To evaluate long-term efficacy of pravastatin, we administered this HMG-CoA reductase inhibitor at a mean dose of 9.9 mg/day to 208 aged patients with serum levels of total cholesterol (TC) over 220 mg/dl (mean +/- SD aged of 70 +/- 7 years; 62 males and 146 females) for 12 months. The mean serum value of TC significantly decreased from the basal level of 265 mg/dl to 216 mg/dl in the 3rd month, and this decrease was maintained throughout the observation period. Similar change was observed in the serum level of low density lipoprotein-cholesterol (LDL-C). Although the mean serum level of high density lipoprotein-cholesterol (HLC-C) in all patients did not change significantly, the HDL-C level in 34 patients with a HDL-C level below 40 mg/dl significantly increased from the 3rd month. The mean serum level of triglyceride (TG) in all patients significantly decreased from the 3rd month, and this decrease in the TG was more prominent in 101 aged patients with TG levels higher than 150 mg/dl. In 168 aged patients on 10 mg/day of pravastatin throughout the period, there were significant negative correlations between the ratio of the decrease in TC in basal serum and each of the basal serum TC levels (r = -0.345, p < 0.001) and age of the subjects (r = -0.208, p = 0.007). These results indicate that long-term administration of pravastatin is effective treatment for lipid metabolism even in aged patients.

Aged↗
PubMed1994

[Therapeutic policy for elderly hypertensives in Japan--a questionnaire survey of specialists].

In order to clarify the therapeutic policy for hypertension in the elderly, we mailed a questionnaire to 147 specialists in Japan and received 123 replies. The upper age limit for antihypertensive treatment was considered to be 80-85 years old by about 50% of the specialists, but the other 50% did not consider an upper age limit. The range of the systolic blood pressure (BP) for which drug treatment was indicated in those without cardiovascular complications was considered to be increased with age, being 160 mmHg and higher in those aged 60-69, 160-170 mmHg and higher in those aged 70-79, and 170-180 mmHg and higher in those aged 80-89, while the level of diastolic BP requiring treatment was considered to be 90-95 mmHg and higher in all age ranges. The goal of BP control was considered to be less than 150/90 mmHg in those aged 60-69, and less than 160/90 mmHg in those aged 70-79 by the majority of the specialists, and to be higher in those aged 80-90, i.e. less than 170-180/95-100 mmHg by more than 20% of the specialists. As the initial selection of antihypertensive regimen, calcium antagonists followed by angiotensin I-converting enzyme inhibitors (ACEI) were selected by the majority, while diuretics, beta-blockers and alpha 1 blockers were chosen by the minority.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Effects of an angiotensin II receptor antagonist, CV-11974, on angiotensin II-induced increases in cytosolic free calcium concentration, hyperplasia, and hypertrophy of cultured vascular smooth muscle cells.

The effects of CV-11974, a potent nonpeptide antagonist of the angiotensin II (AII) type-1 receptor (AT1), on cytosolic free calcium concentration ([Ca2+]i), hyperplasia, and hypertrophy of cultured vascular smooth muscle cells (VSMC) from rat aorta were studied. [Ca2+]i was measured by fura 2, and hyperplasia and hypertrophy were determined by incorporation of [3H]thymidine and [3H]leucine, respectively. CV-11974 had no effect on [Ca2+]i itself, but suppressed 10(-7) M AII-induced increase in [Ca2+]i dose dependently at concentrations from 10(-10) M and completely at 10(-7) M. CV-11974 suppressed both Ca2+ release from intracellular Ca2+ stores and Ca2+ influx from the extracellular space. However, CV-11974 had no effect on the increases in [Ca2+]i induced by prostaglandin F2 alpha (PGF2 alpha), a potent vasoconstrictor, or ionomycin, a Ca2+ ionophore. These results indicate that the suppressive effects of CV-11974 act on the binding of AII and its specific receptors. AII 10(-7) M increased the synthesis of DNA and protein to 1.5 and 1.7 times the control values, respectively. CV-11974 had no effect on synthesis of DNA or protein, but suppressed the AII-stimulated synthesis of DNA and protein dose dependently at concentrations > or = 10(-8) and 10(-10) M, respectively and completely at 10(-6) M. These results indicate that AII increases [Ca2+]i and synthesis of DNA and protein in VSMC through activation of AT1. CV-11974 showed no partial agonistic effects on AII. Thus, CV-11974 may act not only as an antihypertensive agent, but also as an inhibitor of vascular injury stimulated by AII.

Angiotensin II↗
PubMed1994

Assessment of vitamin E nutritional status in neonates, infants and children--on the basis of alpha-tocopherol levels in blood components and buccal mucosal cells.

We examined the age-related changes of alpha-tocopherol levels in various clinically available biosamples in order to assess the vitamin E nutritional status. During the first week of life, more than half of every sample except red blood cells showed alpha-tocopherol levels below the lower limit of normal in a control group of children aged 3-16 years. alpha-Tocopherol levels in mononuclear leucocytes and buccal mucosal cells, which possess LDL receptors, increased in response to the plasma alpha-tocopherol elevation within a week after birth. However, RBC and platelet levels did not respond so quickly. Considering the transfer of tocopherol into body tissues during LDL catabolism, the determination of tocopherol levels in cells with LDL receptors may be useful for assessing the vitamin E status and our present study suggests that the tissue vitamin E status may be marginal in neonates.

Adolescent↗