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S Takata

Publications and source records attributed to S Takata.

At least 145 records · Page 8Linked to original sources
PubMed1988

Molecular mechanism of action by atrial natriuretic peptide in rat vascular smooth muscle cells.

The mechanism by which atrial natriuretic peptide (ANP) acts on cells remains obscure. Using cultured vascular smooth muscle cells (VSMC) from rat aorta, we studied the structure-activity relationship of alpha-human(h) ANP and attempted to clarify its cellular mechanism of action. Binding studies using a variety of synthetic alpha-hANP analogs with deletion and substitution of amino-acid residue(s) within the ring structure and deamino-dicarba analogs with replacement of the disulfide bond with an ethylene linkage, suggested that the original cyclic structure is a minimum requirement for biological activity and the disulfide bond is not essential for receptor binding. The present study using VSMC loaded with a fluorescent Ca2+ indicator quin-2 revealed that alpha-rat(r) ANP has no effect on increases in cytosolic free Ca2+ concentration stimulated by angiotensin (A) II or arginine-vasopressin (AVP). While both vasoconstrictive hormones rapidly stimulated phosphatidylinositol (PI) response in VSMC, pretreatment with rANP did not affect AII- or AVP-induced PI response. However, AII-stimulated phosphorylation level of 20 K-dalton (Da) myosin light chain (MLC), a regulatory contractile protein of VSMC, was attenuated by pretreatment with rANP. These data suggest that ANP may not act at site of either agonist-induced membrane PI hydrolysis or intracellular Ca2+-signal system, but may partly be involved in phosphorylation/dephosphorylation of 20 K-Da MLC in cultured rat VSMC.

Angiotensin II↗
PubMed1988

Concomitant increase in cytosolic free calcium and phosphorylation of myosin light chain by vasoconstrictive hormones in cultured rat vascular smooth muscle cells.

Using the fluorescent Ca2+ indicator quin-2 to measure the cytosolic Ca2+ concentration [( Ca2+]i) and glycerol-urea polyacrylamide gel electrophoresis combined with radioimmunoblotting to assess phosphorylation of 20 k-dalton (Da) myosin light chain (MLC), the effects of angiotensin (A) II and arginine-vasopressin (AVP), both potent vasoconstrictive hormones, on changes in [Ca2+]i and phosphorylation levels of 20 k-Da MLC were studied in cultured rat vascular smooth muscle cells (VSMC). AII and AVP induced immediate (within 1 min) and dose-dependent increases in both [Ca2+]i and phosphorylation of 20 k-Da MLC. Pretreatment of VSMC with AII receptor antagonist and V1 receptor antagonist, completely blocked increases in [Ca2+]i by AII and AVP, respectively. Phosphorylation of 20 k-Da MLC stimulated by these agonists was also inhibited by their specific antagonists. These data suggest that receptor-mediated increases in [Ca2+]i by AII and AVP are closely associated with phosphorylation of 20 k-Da MLC in VSMC. The present methods should provide a suitable in vitro cell model for investigation of the molecular mechanism by which vasoactive hormones act on cells to induce contraction of vascular smooth muscle.

Aminoquinolines↗
PubMed1988

Effects of insulin on vasoconstrictive responses to norepinephrine and angiotensin II in rabbit femoral artery and vein.

To determine whether insulin has a vasodilator action on the artery and vein, the effects of insulin at varying concentrations (120 microU/ml, 1.2 mU/ml, 12 mU/ml, and 120 mU/ml) on vasoconstriction by norepinephrine (NE) and angiotensin II (ANG II) were studied in the isolated rabbit femoral artery and vein. Helical strips were suspended in an organ bath filled with modified Krebs solution (pH 7.4), were gassed with 95% O2/5% CO2 at 36 degrees C, and isotonic contractions were measured. Insulin significantly and dose dependently inhibited the vasoconstriction induced by NE (10(-8) M for the artery and 10(-7) M for the vein) at greater than or equal to 1.2 mU/ml for both the artery and vein and the vasoconstriction induced by ANG II (3 x 10(-10) M for the artery and 3 x 10(-9) M for the vein) at greater than or equal to 1.2 mU/ml for the artery and greater than or equal to 12 mU/ml for the vein. The results indicate that insulin has an inhibitory effect on NE- and ANG II-induced contraction in both the artery and vein, and this appeared to be a contributory factor in the hypotensive effect observed in diabetic patients treated with insulin.

Angiotensin II↗
PubMed1988

On the factors influencing the dispersion of radioiodines.

Radioactivities dispersed from 0.1 N sodium hydroxide solutions of 123I, 125I, or 131I were measured, and the factors influencing dispersion of radioiodines were analyzed. The radioiodines dispersed were trapped by glass fiber filters, charcoal filters, and separable paint. The factors influencing the dispersion of radioiodines are discussed in terms of the dispersal rate, which defined as the ratio of total activity of three kinds of traps in a unit time to whole activity. In order to clarify the factors influencing the dispersal rate, we carried out the experiments; on the effect of reducing agent, that of radioactive concentration of radioiodine, that of mixing the 125I solution with 131I, and that of scavenging hydrated electrons and hydroxyl radicals. It could be concluded from experimental results that the principal factors influencing dispersion of radioiodines are the number of atoms of radioiodine per volume and the energy absorbed in solution from radioiodines. In regard to the absorbed energy, we thought that the dispersion of radioiodines is influenced mainly by hydrated electron, not markedly by hydroxyl radical.

Iodine Radioisotopes↗
PubMed1987

Ventricular myocytes from neonatal rats are more responsive to dexamethasone than atrial myocytes in synthesis of atrial natriuretic peptide.

Using the primary culture of neonatal rat ventricular myocytes, synthesis and secretion of rat atrial natriuretic peptide (rANP) were studied. Ventricular myocytes in culture, although contained less amounts of cellular immunoreactive (IR)-rANP, secreted substantial amounts of IR-rANP at a rate comparable to that of atrial myocytes. Dexamethasone markedly stimulated synthesis and secretion of IR-rANP by cultured ventricular myocytes in a dose-dependent manner (10(-10)-10(-6) M), of which effect was far more potent than that in atrial myocytes. Testosterone and triiodothyronine also stimulated synthesis and secretion of ventricular IR-rANP to the extent comparable to that of atrial IR-rANP. The present study suggests that tissue-dependent difference in glucocorticoids sensitivity plays an important role in the regulation of developmental ANP gene expression in mammalian heart.

Age Factors↗
PubMed1987

Binding of synthetic beta-human atrial natriuretic peptide to cultured rat vascular smooth muscle cells.

We have studied the effects of synthetic beta-human atrial natriuretic peptide (beta-hANP), an antiparallel dimer of alpha-hANP, on receptor binding and cGMP generation in cultured rat vascular smooth muscle cells and compared the effects with those of alpha-hANP. Characteristics of temperature-dependent binding and degradation of 125I-beta-hANP were similar to those of 125I-alpha-hANP. Scatchard analysis indicated a single class of binding sites for beta-hANP with a maximal binding capacity one-half that of alpha-hANP. Parallel and antiparallel dimers were equipotent in inhibiting the binding and stimulating intracellular cGMP formation, of which the maximal effect was about one-half that of alpha-hANP. Reverse-phase high performance liquid chromatography revealed that most of beta-hANP added to cells was converted to a small molecular mass component corresponding to alpha-hANP after incubation. These data suggest that the less potent effect of beta-hANP in receptor binding and cGMP generation may be partly accounted for by the possible conversion of beta-hANP to alpha-hANP at the site of target cells.

Animals↗
PubMed1987

Effects of steroid and thyroid hormones on synthesis of atrial natriuretic peptide by cultured atrial myocytes of rat.

The in vitro effects of various steroid and thyroid hormones on synthesis of rat atrial natriuretic peptide (rANP) were studied using new-born rat atrial myocytes in culture. Dexamethasone, testosterone and triiodothyronine markedly stimulated both synthesis and secretion of immunoreactive (IR)-rANP with the same peak after 4-day-culture. Dexamethasone and testosterone dose-dependently (10(-7)-10(-6) M) stimulated synthesis of IR-rANP and were the most potent among various steroids tested. Triiodothyronine (T3) also stimulated synthesis of IR-rANP in a dose-dependent manner (10(-8)-10(-7) M), of which effect was more potent than that of tetraiodothyronine, whereas reverse T3 was ineffective. The present study clearly shows that glucocorticoids, androgens and thyroid hormones directly stimulate synthesis of ANP by atrial myocytes and suggests that ANP may play a potential role in mediating and/or modulating the biological effects by these hormones in the cardiovascular system.

Adrenal Cortex Hormones↗
PubMed1987

Down-regulation of atrial natriuretic peptide receptor and cyclic GMP response in cultured rat vascular smooth muscle cells.

Treatment of cultured rat vascular smooth muscle cells with human atrial natriuretic peptide (hANP) or Met(O)12hANP caused a similar and marked reduction (approximately 80%) of ANP receptor number (down-regulation). A second challenge with hANP stimulated the accumulation of intracellular cGMP in the down-regulated cells to the same extent as in control cells. These data suggest that ANP receptor sites are functionally heterogenous, the more abundant site being uncoupled from guanylate cyclase but susceptible to down-regulation.

Animals↗
PubMed1987

Effects of calcium-antagonists and calmodulin inhibitors on DNA synthesis in cultured rat vascular smooth muscle cells.

To investigate the role of intracellular Ca2+ in the mechanism of cellular proliferation of vascular smooth muscle cells (VSMC), the effects of Ca2+-antagonists and calmodulin (CaM) inhibitors on DNA synthesis stimulated by serum-derived growth factors were studied in cultured VSMCs derived from rat aorta. DNA synthesis assessed by incorporation of [3H]thymidine into the cells was significantly stimulated by epidermal growth factor (EGF), platelet-derived growth factor (PDGF) or fetal bovine serum (FBS), of which the effects were dose-dependently inhibited by a variety of Ca2+-antagonists, such as verapamil, diltiazem and nicardipine. Trifluoperazine and W-7, both specific CaM inhibitors, similarly inhibited DNA synthesis stimulated by EGF, PDGF or FBS in a dose-dependent manner, whereas W-5, a less specific CaM inhibitor, was minimally effective. These data suggest that the Ca2+-CaM system plays an important role in the mechanism of growth factor-induced DNA synthesis in VSMCs.

Animals↗
PubMed1987

Abnormal cardiopulmonary baroreflexes in normotensive young subjects with a family history of essential hypertension.

Cardiopulmonary baroreflex control of forearm vascular resistance (FVR) and arterial baroreflex control of heart rate were compared between 12 normotensive subjects with hypertensive relatives (group A, 19.4 +/- 0.2 years) and 12 normotensive subjects with no family history of hypertension (group B, 19.5 +/- 0.3 years). Cardiopulmonary baroreflexes were evaluated using lower body negative pressure (LBNP) at -20 mmHg, and arterial baroreflexes were measured by Oxford phenylephrine method. Resting arterial pressure, central venous pressure, heart rate, cardiac index, total peripheral resistance, and FVR were not different between the two groups. Arterial baroreflex slope (BS) and reflex increases in FVR during LBNP were significantly lower in group A than in group B (11.4 +/- 0.9 vs. 17.1 +/- 1.1 ms/mmHg, 37.7 +/- 8.1% vs. 86.5 +/- 18.7%, respectively). There was significant correlation between %FVR and BS (r = 0.59; p less than 0.01). These results suggest that both cardiopulmonary and arterial baroreflexes are impaired in normotensive young subjects with a family history of hypertension.

Adolescent↗
PubMed1986

Regulation of atrial natriuretic peptide receptors in cultured vascular smooth muscle cells of rat.

To elucidate the regulation of vascular receptors for atrial natriuretic peptide (ANP), we have studied the binding capacity of 125I-labeled rat (r) ANP using cultured vascular smooth muscle cells from rat aorta. After preincubation with 3.2 X 10(-8) M rANP at 37 degrees C, the binding capacity decreased as a function of time; the maximal receptor loss (70-75%) occurred after 4 hrs and persisted for 24 hrs. Pretreatment with cycloheximide (20 micrograms/ml) and actinomycin D (2 micrograms/ml) similarly caused a dramatic reduction (approximately 80%) of the binding capacity after 24 hrs; the half-life (t1/2) of the receptor loss was approximately 7-8 hrs. Following removal of rANP, the "down-regulated" ANP receptors fully recovered in the presence of 10% fetal calf serum, but not in combination with either actinomycin D or cycloheximide. Concanavalin A dose-dependently inhibited the binding. The binding capacity also decreased with time in the presence of tunicamycin (1 microgram/ml) with t1/2 of approximately 30 hrs. These data indicate that protein and carbohydrate moieties are essential for the functional integrity of the vascular receptor binding sites for ANP, and suggest that the recovery of the receptor loss by "down-regulation" requires concomitant RNA and protein synthesis.

Animals↗
PubMed1986

A family with myotonic dystrophy associated with diffuse cardiac conduction disturbances as demonstrated by His bundle electrocardiography.

In a family with myotonic dystrophy, three siblings showing ECG abnormalities were subjected to His bundle ECG studies. The duration of the disease ranged from 9 to 24 years. All three siblings had prolonged HV intervals (His-Purkinje conduction times) of 70 to 80 msec. The sister with the shortest duration of the disease had second-degree atrioventricular (AV) nodal block as well as left posterior fascicular block, the younger brother had left anterior fascicular block, and the elder brother with the longest history had first-degree AV block without bundle branch or fascicular block. With regard to associated arrhythmias, however, the elder brother developed paroxysmal ventricular tachycardia, apparently due to reentry involving the right bundle branch system, whereas the younger brother and sister had sinus bradycardia alone. This study reveals the prevalence of diffuse conduction disturbances of the specialized conducting system in a family with myotonic dystrophy.

Adult↗
PubMed1986

Effect of propranolol on baroreflex control of heart rate in young patients with essential hypertension.

The effect of propranolol on baroreflex control of heart rate was studied in 12 young patients with essential hypertension and was compared with that of 12 age-matched normotensive subjects. Resting heart rate and cardiac index in patients with essential hypertension were significantly higher than those of control subjects (p less than 0.001, p less than 0.01, respectively). The reduction of heart rate and cardiac index after propranolol were significantly greater in patients with essential hypertension than in control subjects (p less than 0.01, p less than 0.05, respectively). In the control state, the baroreflex slope in young patients with essential hypertension was significantly less than that of control subjects (p less than 0.01). After propranolol, the baroreflex slope was significantly increased in control subjects (p less than 0.01), but remained unchanged in patients with essential hypertension. These results suggest, first that the antihypertensive action of propranolol must be due to a mechanism other than the augmented baroreflex function and, second that increased beta-adrenergic activity is not a factor contributing to impaired baroreflex function in young patients with essential hypertension.

Adult↗
PubMed1986

Effects of insulin on pressor responsiveness and baroreflex function in diabetes mellitus.

The effects of insulin on pressor responsiveness to alpha agonist (phenylephrine) and angiotensin II, and baroreflex function were studied in fifteen diabetic patients without autonomic neuropathy. The dose of phenylephrine required to increase systolic pressure by 25 mmHg (PD25) was significantly increased from 38 +/- 7 to 62 +/- 9 micrograms (p less than 0.05) after IV injection of 4 U of Actrapid monocomponent insulin. The dose of angiotensin II required to increase systolic pressure by 30 mmHg (AD30) was also increased from 0.29 +/- 0.07 to 0.48 +/- 0.10 micrograms (p less than 0.01). Following insulin administration, the dose-response curves for phenylephrine and angiotensin II were shifted to the right. The baroreflex sensitivity was not affected by insulin. In contrast, there was no significant change in PD25, AD30 or baroreflex sensitivity after the injection of saline. These results suggest that insulin attenuates the pressor responsiveness to alpha agonist and angiotensin II, which may be one of the significant mechanisms in insulin-induced vasodilation.

Adult↗
PubMed1986

Multiple endocrine neoplasia with Cushing's syndrome due to paraganglioma producing corticotropin-releasing factor and adrenocorticotropin.

A male patient with corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH)-producing syndrome is described. Soon after being referred to us the patient developed pneumonia, anaemia, oedema and respiratory distress, and died on the 24th day after admission. Autopsy and histology revealed that he had a rare type of multiple endocrine neoplasia (type 1 + paraganglioma) with a mediastinal paraganglioma, parathyroidal hyperplasia, pancreatic islet cell adenoma, duodenal multiple carcinoid tumours and adrenocortical nodular hyperplasia. It was not possible to examine the pituitary. The paraganglioma contained a large amount of immunoreactive (IR)-CRF (606 ng/g wet weight), IR-ACTH (59.4 ng/g wet weight), IR-human proopiomelanocortin n-terminal (1-76) peptide (hNT, 156.8 ng/g wet weight) and IR-beta-lipotropin (beta-LPH, 146.9 ng/g wet weight). The major IR-ACTH, beta-LPH and IR-hNT were eluted at ACTH-(1-39), beta-LPH and hNT marker positions, respectively. Big ACTH was not detected. IR-CRF eluted at the human CRF marker position on Sephadex G-75 chromatography and high performance liquid chromatography (HPLC). The IR-CRF fraction from the HPLC showed CRF bioactivity which paralleled that of synthetic human CRF in monolayer cultured rat anterior pituitary cells. Our results suggest that not only ACTH but CRF produced by the paraganglioma was responsible for the patient's Cushing's syndrome.

Adrenocorticotropic Hormone↗