Search PubMed⌕ Search

Biomedical subjects

Y Nara

Publications and source records attributed to Y Nara.

At least 163 records · Page 9Linked to original sources

Enhanced growth rate of cultured smooth muscle cells from spontaneously hypertensive rats.

Smooth muscle cells were isolated and cultured from the aortic media of age-matched, stroke-prone and stroke-resistant spontaneously hypertensive rats (SHRSP, SHRSR:SHRs) and Wistar-Kyoto rats (WKY), and the growth rate of cells from the three strains was compared. Under electron microscopical observation the cells were identified as modified (or synthetic-type) smooth muscle cells. Cells occurring at low densities showed the same morphology for both SHRs and WKY, but cells occurring at higher densities were observed to be smaller in SHRs than in WKY. An analysis of the growth curves of cells showed a significantly enhanced replication rate in cells from SHRs compared with those from WKY, especially in the early passages. In later passages (repeated until the 9th passage), however, this distinction was not clear. These growth characteristics were also confirmed in cells from both 12- and 24-week-old, age-matched SHRs and WKY. We could not find any difference between the growth characteristics of cells from SHRSP and SHRSR. It is possible to hypothesize from these findings that the abnormality relating to hypertension (hypertension being a common characteristic of SHRSR and SHRSP) is found in the smooth muscle cells, and is reflected as an enhanced growth rate when they are exposed to mitogenic stimuli, such as in atherosclerosis.

Animals↗

Phorbol 12-myristate 13-acetate prevents isoproterenol-induced morphological change in cultured vascular smooth muscle cells.

The effect of phorbol 12-myristate 13-acetate (PMA) on isoproterenol (ISO)- and dibutyryl cAMP (dBcAMP)-induced morphological change and cytoskeletal reorganization was studied in cultured vascular smooth muscle cells (VSMC) using the fluorescence staining of actin and microtubules. The treatment of VSMC with 1.0 microM of ISO or with 1.0 mM of dBcAMP for 90 min induced the disruption of actin-containing stress fibers followed by cytoplasmic arborization. The addition of 100 or 10 nM of PMA prevented both the destruction of actin fibers and cell arborization induced either by ISO or by dBcAMP. However, PMA rather enhanced cAMP production stimulated by ISO. 1-Oleoyl-2-acetyl-sn-glycerol (100 micrograms/ml) mimicked this inhibitory effect of PMA whereas 4 alpha-phorbol 12,13-didecanoate (100 nM) failed to block the arborization. These results indicated that the inhibition of arborization by PMA was mediated through the activation of protein kinase C. Colchicine at 5.0 microM also had an inhibitory effect on ISO- and dBcAMP-induced cell arborization. However, immunofluorescence studies revealed that colchicine but not PMA elicited the reorganization of microtubules, suggesting that the effect of PMA was mediated through a mechanism different from that of colchicine. These observations indicated that the morphology of VSMC was regulated through the alteration of cytoskeletal organization induced by cAMP-mediated and by protein kinase C-dependent systems.

Actin Cytoskeleton↗

Characteristics of "embryoid body" in human gonadal germ cell tumors.

The characteristics of so-called "embryoid body" appearing in gonadal germ cell tumors were studied histologically and immunohistochemically on serial sections of three cases (one ovary and two testes). The embryoid bodies were usually observed to be contiguous with immature or mature intestinal ducts, hepatic nests, or epidermal cell nests on serial sections, though they appeared to be isolated in one section. The "amniotic cavity"-like structure of embryoid body was continuous with intestinal duct, and rarely with squamous cell nests, while the "yolk sac" was continuous with hepatic tissue. In these immature or mature structures, differentiation was always found independently of "disc," and portions of "ectoderm" and "endoderm" remained less differentiated in comparison with others. These findings were in contrast with a normal embryo in which immature and/or mature structures are derived from the embryonic disc. The amniotic cavity connected frequently with yolk sac. From the present results, the embryoid body is not considered to be a real or teratomatous embryo, but only a product during a divergent differentiation into intestine and liver from the plastic epithelium, which seems to be derived from an embryonic gut.

Adult↗

A new approach to the prevention of hypertensive cardiovascular diseases by controlling the proliferation of vascular smooth muscle cells.

Cholera toxin subunit B suppressed the proliferation of cultured vascular smooth muscle cells from the thoracic aorta of Wistar-Kyoto rats (WKY), stroke-resistant spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP). Since cholera toxin subunit B did not stimulate cyclic AMP accumulation in vascular smooth muscle cells, the effect of cholera toxin subunit B might be due to another mechanism. Cholera toxin subunit B bound to the surface of vascular smooth muscle cells and was rapidly incorporated into them. The morphological structure of vascular smooth muscle cells was transformed from the synthetic type to the non-synthetic type, in which microfilaments and intermediate filaments were abundantly formed, while rough endoplasmic reticulum was decreased after CTB treatment.

Animals↗

Coenzyme Q10 content in different parts of the normal human heart.

Coenzyme Q10 (CoQ10) and citrate synthase (CS) activities were analysed in the myocardium of brain-dead organ donors (14-40 years). Different parts of the heart were studied: right and left auricular appendage, right and left atrium, right ventricle (septum and free wall) and left ventricle (septum, free wall, and papillary muscle). Freeze-dried, dissected myocardial samples were analysed for CoQ10 content by HPLC and CS activity by fluorometric technique. CoQ10 content in the normal human myocardium was lowest in auricular appendages and atria (0.25 +/- 0.06 mg X g-1 dry muscle), intermediate in right ventricle (0.37 +/- 0.05 mg X g-1 dm) and highest in left ventricle (0.42 +/- 0.07 mg X g-1 dm). CS activity showed the same relationship between these locations as CoQ10. The results suggest that there exist differences in CoQ10 content between different parts of the normal human myocardium. These differences were closely related to the differences in CS activity between corresponding parts. The differences between different parts of the heart may be related to divergent work demand, and the constant relationship between CS and CoQ10 may be related to their coupling to the mitochondrial oxidative metabolism.

Adult↗

Cellular mechanisms of hypertension and atherosclerosis: hypoxia-induced lipid accumulation in cultured vascular smooth muscle cells from the stroke-prone spontaneously hypertensive rat.

The effects of hypoxia on the lipid metabolism of cultured vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats (SHRSP) were examined. The total cholesterol in smooth muscle cells cultured with hyperlipidaemic serum reached higher levels under hypoxic conditions (3.5% O2, 5.0% CO2, 91.5% N2) than under normal conditions (20% O2, 5.0% CO2, 75% N2). In normal serum, cholesterol increased slightly under hypoxic conditions. No difference was noted in cholesterol synthesis from [14C]-acetic acid. Triglyceride levels in smooth muscle cells cultured with hyperlipidaemic serum and normal serum were significantly increased compared with fetal calf serum. The increase in triglyceride levels was inhibited markedly under hypoxic conditions. Triglyceride synthesis induced by normal serum in the hypoxic cells was decreased compared with control cells. The metabolic rate of triglyceride did not differ between the two. These results indicate that hypoxic conditions accelerate the cellular uptake of cholesterol, an initial step in atherogenesis.

Animals↗

Significance of biological parameters of human blood levels of CoQ10.

Ninety-one men and 143 women who were so-called normal subjects were tested for cardiac performance at rest and their blood levels of co-enzyme Q10 (CoQ10) were determined. In males, a negative relationship between progression of age and cardiac performance, and a positive relationship between progression of age and blood levels of CoQ10 were revealed. In females, a positive relationship between age and blood levels of CoQ10 was found. The mean CoQ10 blood level for both sexes was the same (0.79 +/- 0.20 micrograms/ml for males and 0.79 +/- 0.23 for females). Cardiac performance declines with age in the male population. A decreased biosynthesis and/or incorporation of CoQ10 into mitochondrial structures of muscle cells may occur with age in a normal population.

Adult↗

Effect of extracellular calcium on vascular contraction induced by phorbol ester.

In rat thoracic aorta, 12-0-tetradecanoyl-phorbol-13-acetate (TPA) caused a slowly onset, sustained vascular contraction. The contraction was markedly reduced in the absence of extracellular Ca2+, although small tension development was still observed. The tension developed by TPA in the presence of Ca2+ was decreased by serial addition of a Ca2+-channel blocker, verapamil in a concentration-dependent manner. TPA could cause vascular contraction to almost maximum level at lower concentration of extracellular Ca2+, compared with KCl- or norepinephrine-induced contraction. These results suggest that extracellular Ca2+ which influxes through Ca2+-channels into cytoplasm is necessary for full tension development by TPA, and that TPA increases sensitivity of contractile mechanisms coupling with Ca2+.

Animals↗

New establishment of hypertensive diabetic animal models: neonatally streptozotocin-treated spontaneously hypertensive rats.

Hypertensive diabetic animal models have been developed by injecting streptozotocin (STZ) in neonatal stroke-resistant spontaneously hypertensive rats (SHRSR) and stroke-prone SHR (SHRSP) at the age of two days. After the treatment, the animals showed mild insulin deficiency and mild hyperglycemia at the age of three to four months. Diabetic nephropathy was produced particularly in STZ-treated SHRSR at the age of six months. The effect of neonatal STZ injection on hyperglycemia varied among normotensive Wistar-Kyoto rats (WKY), SHRSR, and SHRSP; SHRSR showed the highest glucose levels, SHRSP showed intermediate levels, and WKY was the lowest. All STZ-treated SHRSR showed glycosuria, while glycosuria was not observed in the treated SHRSP and WKY. Histologic study indicated that these strain differences were partly ascribed to differences in islet B-cell sensitivity to toxic effects of STZ. The development of hypertension was not accelerated in these SHRSR and SHRSP compared with respective nontreated controls. Since STZ-treated SHRSR develop mild diabetic symptom with hypertension and develop mild diabetic glomerulosclerosis, they are good models for studying vascular complications or other problems relating to the synergism between hypertension and diabetes mellitus.

Animals↗

Mechanisms for the inhibition of vasopressin-stimulated water flow by captopril in the toad bladder.

The mechanisms by which captopril inhibits vasopressin-stimulated osmotic water flow in the toad bladder have been investigated in vitro. Captopril has two possible mechanisms for the inhibitory action on the water flow, one is its stimulative effect on prostaglandin E2 (PGE2) biosynthesis by inhibition of kininase II activity, the other, is a direct effect on water flow independent of PGE2. Captopril inhibited the vasopressin-, cyclic adenosine monophosphate- and 3-isobutyl-1-methyl-xanthine-stimulated water flow. The inhibition of water flow by bradykinin was enhanced by captopril. These data indicate that captopril increased the amount of bradykinin in toad bladder cells resulting in the production of PGE2 which inhibited the increase in water flow induced by vasopressin. The inhibitory effect of captopril, however, also occurred in the presence of indomethacin, when the production of PGE2 was attenuated. Thus, it was concluded that captopril inhibits the vasopressin-stimulated water flow indirectly by inhibiting the degradation of bradykinin and thereby enhancing the production of PGE2, and directly at a site following the production of cyclic adenosine monophosphate by vasopressin.

1-Methyl-3-isobutylxanthine↗

Effect of milk protein and fat intake on blood pressure and the incidence of cerebrovascular diseases in stroke-prone spontaneously hypertensive rats (SHRSP).

The intake of two milk protein-rich diets containing casein and whey protein attenuated the development of severe hypertension in stroke-prone spontaneously hypertensive rats (SHRSP), and extended their life span in comparison with SHRSP on a regular stock diet. Milk fat-rich diet intake reduced the incidence of cerebrovascular disease in SHRSP without a significant fall in blood pressure. These results suggest that certain milk components have a preventive effect on hypertension and cerebrovascular disease in SHRSP.

Animals↗

Effect of calcium antagonists on hypertension and diabetes in new hypertensive diabetic models.

Hypertension in diabetic patients is more common than in controls, contributes substantially to their increased cardiovascular morbidity and mortality, and should be treated as accurately as diabetes mellitus itself. The purpose of this study was to investigate the effect of calcium antagonists on hypertension and diabetes in hypertensive diabetic rats, which were newly established by neonatal injection of streptozotocin in spontaneously hypertensive rats. At the age of 6 months, hypertensive diabetic rats and control hypertensive nondiabetic rats were treated with hydralazine, diltiazem, or nifedipine for 2 months. In diabetics, antihypertensive therapy not only prevented the progression of nephropathy but also improved glucose metabolism by increasing insulin secretion. Calcium antagonists in this study reduced urinary protein excretion, and nifedipine relieved hypoalbuminemia. Hydralazine had no beneficial effect on urinary protein excretion. Calcium antagonists as compared to hydralazine decreased the heart weight. Calcium antagonists have a beneficial effect on cardiac hypertrophy. Good correlations have been found between kidney weight and blood pressure in hypertensive diabetic rats. It is suggested that blood pressure reflects increase in kidney weight in diabetic patients.

Animals↗

Effects of sulphur amino acids on the development of hypertension and atherosclerosis in stroke-prone spontaneously hypertensive rats.

We investigated the effects on blood pressure of 5% taurine administered prenatally or postnatally via maternal parents in stroke-prone spontaneously hypertensive rats (SHRSP). Prenatal and/or postnatal administration of taurine produced a blood pressure reduction in the offspring until at least 3 months of age. Furthermore, offspring exposed to high concentrations of taurine through the placenta during the prenatal period and also for 1 month after birth via maternal milk, showed a greater reduction in blood pressure than the group given taurine prenatally but not postnatally. The stroke-prone SHR were fed a high-fat cholesterol and low-protein diet containing 1% methionine or with 3% lysine in drinking water, and effects of the dietary amino acids on the development of atherogenesis were investigated. Intake of additional 1% methionine or 3% lysine had marked preventive effects on atherogenesis in the cerebral and mesenteric arteries in SHRSP. Therefore, early dietary intake of sulphur amino acids delays the onset of hypertension and attenuates the development of both severe hypertension and atherosclerosis in SHRSP.

Animals↗

Catecholamine-induced polyploidization in vascular smooth muscle cells.

Polyploidy formation of vascular smooth muscle cells was observed in vivo by intravenous infusion of norepinephrine or epinephrine in Wistar-Crea rats for 12 days at the rate of 0.02 mumol/hr with an osmotic minipump and in vitro by exposing cultured vascular smooth muscle cells obtained from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) to norepinephrine (10(-7)M to 10(-5)M) in the cultured medium. Infusion in vivo of norepinephrine but not epinephrine increased blood pressure slightly. However, both agents increased significantly the frequency of tetraploidy of smooth muscle cells up to 14.9 +/- 0.6% (mean +/- SE) and 9.2 +/- 0.5% compared with saline (6.5 +/- 0.7%). Exposure in vitro to norepinephrine (10(-6)M) increased the frequency of tetraploidy and octaploidy of smooth muscle cells from SHR up to 14.2% and 2.1%, respectively, compared with nonexposed cells (8.1% and 0.2%). These results appear to indicate that norepinephrine and epinephrine induce polyploidy of smooth muscle cells independently from blood pressure elevation.

Animals↗