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POTENTIATION OF VASCULAR-RESPONSES TO CATECHOLAMINES BY POR-8

JOURNAL OF DENTAL RESEARCH 1975年第NB期54卷 B63-B67页

作者： WATERSON, JG UNIV WESTERN AUSTRALIA FAC DENT SCI179 WELLINGTON STPERTH 6000WESTERN AUSTRALAUSTRALIA

The study investigated the potentiating effect of a polypeptide vasoconstrictor ornithine vasopressin (POR-8) on the constriction of vascular smooth muscle by epinephrine and followed an investigation of the interactions of POR-8 and norepinephrine. The main purpose of the study was to investigate the feasibility of using mixtures of POR-8 and epinephrine in local anesthetic solutions. This could theoretically reduce side effects by producing adequate vasoconstriction with lower concentrations of epinephrine. To allow comparison and to assist in presentation, some methodology and results of the norepinephrine study are included.

关键词：动脉/药物作用血管/药物作用剂量效应关系药物药物协同作用耳/血液供给肾上腺素/投药和剂量肾上腺素/药理学肌平滑/药物作用去甲肾上腺素/投药和剂量去甲肾上腺素/药理学鸟氨酸/药理学血管升压素类/药理学动物兔

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The kinase inhibitor fasudil (HA-1077) reduces intimal hyperplasia through inhibiting migration and enhancing cell loss of vascular smooth muscle cells

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1999年第1期262卷 211-215页

作者： Negoro, N Hoshiga, M Seto, M Kohbayashi, E Ii, M Fukui, R Shibata, N Nakakoji, T Nishiguchi, F Sasaki, Y Ishihara, T Ohsawa, N Osaka Med Coll Dept Internal Med 1 Takatsuki Osaka 5698686 Japan Asahi Chem Ind Co Ltd Life Sci Res Ctr Frontier 21 Project Shizuoka 4160934 Japan

Smooth muscle cell (SMC) migration plays an important role in restenosis after angioplasty, Myosin phosphorylation is necessary for cell migration. Fasudil is an inhibitor of protein kinases, including myosin light chain kinase and Rho associated kinase, thereby inhibiting myosin phosphorylation, and it has been clinically used to prevent vasospasm following subarachnoid hemorrage, Based on these findings, we examined the antimigrative action of fasudil. In SMC (SM-3), fasudil (1-100 mu M) inhibited SMC migration in a dose-dependent man ner (p < 0,001), Fasudil suppressed actin stress fiber formation dose dependently. In rabbit carotid artery, fasudil (10 mg/kg/day) markedly reduced intimal hyperplasia 14 days following balloon injury. Cell kinetic study showed that fasudil did not affect proliferation but enhanced cell loss in the media after injury. We concluded that fasudil reduced neointimal formation after balloon injury through both inhibiting migration and enhancing cell loss of medial SMC. (C) 1999 Academic Press.

关键词：肌动蛋白类/代谢主动脉气囊扩张术颈动脉损伤细胞计数/药物作用细胞分裂/药物作用细胞运动/药物作用细胞培养的剂量效应关系药物增生/病理学微丝/药物作用微丝/代谢肌平滑血管/细胞学肌平滑血管/药物作用肌平滑血管/损伤肌平滑血管/病理学蛋白激酶抑制剂时间因素血管内膜/药物作用血管内膜/损伤血管内膜/病理学伤口愈合/药物作用动物人类男(雄)性兔

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Thrombospondin-1, a natural inhibitor of angiogenesis, is present in vitreous and aqueous humor and is modulated by hyperglycemia

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2000年第1期267卷 257-261页

作者： Sheibani, N Sorenson, CM Cornelius, LA Frazier, WA Washington Univ Sch Med Dept Biochem & Mol Biophys St Louis MO 63110 USA Washington Univ Sch Med Div Dermatol St Louis MO 63110 USA

Negative regulators of angiogenesis play a major role in maintaining vascular homeostasis. Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. This report examines the presence of TSP1 in ocular samples and determines whether its production is altered in diabetes. Western blot analysis detected a 140 kDa antiangiogenic fragment of TSP1 (gp140) in vitreous samples prepared from normal human and rat eyes. Intact TSP1 was detected in aqueous humor samples prepared from normal rat and bovine eyes. In contrast, TSP1 was virtually absent in vitreous and aqueous humor samples prepared from diabetic rat eyes. Furthermore, production of TSP1 by microvascular endothelial cells in culture was sensitive to high concentrations of glucose. Retinal blood vessels appeared nonuniform and dilated in diabetic animals when compared to control animals. These results demonstrate that TSP1 and its antiangiogenic fragment are present in aqueous humor and vitreous of normal rat eyes and are dramatically reduced in diabetes. Thus, TSP1 may play a role in ocular vascular homeostasis and its absence may contribute to vascular dysfunctions associated with diabetes. (C) 2000 Academic Press.

关键词：眼房水/细胞学眼房水/生理学细胞培养的糖尿病实验性/病理学糖尿病实验性/病理生理学内皮血管/药物作用内皮血管/生理学葡萄糖/药理学高血糖症/病理生理学微循环/生理学大鼠 Sprague-Dawley 参考值视网膜血管/生理学视网膜血管/病理生理学凝血酶敏感蛋白1/分析凝血酶敏感蛋白1/生理学脐静脉玻璃体/细胞学玻璃体/生理学动物牛人类男(雄)性大鼠

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Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy postmenopausal women

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第11期85卷 1297-1301页

作者： Simons, LA von Konigsmark, M Simons, J Celermajer, DS Univ New S Wales Lipid Res Dept St Vincents Hosp Darlinghurst NSW 2010 Australia Royal Prince Alfred Hosp Dept Cardiol Sydney NSW Australia

Plant estrogen or phytoestrogens (PE) are increasingly consumed for the purposes of menopause symptom relief and prevention of cardiovascular and other diseases. The objective of this study was to evaluate the effects of PE on plasma lipids and lipoproteins and on endothelial function. Twenty healthy, postmenopausal women, 50 to 70 years old, and with evidence of endothelial dysfunction, were treated with a soybean PE tablet of 80 mg/day of isoflavones, Endothelial function was assessed noninvasively using brachial ultrasound. A double-blind, placebo-controlled, randomized crossover design was employed. After 3 weeks stabilization on a standard fat-reduced diet, subjects received PE or placebo for 8 weeks in random order, separated by a washout period of 8 weeks. Compared with placebo, there were no significant effects of PE on blood pressure and plasma lipid or lipoprotein concentrations. Flow-mediated endothelium-dependent dilation (FMD) in response to reactive hyperemia was not significantly changed by PE ingestion (3.3 +/- 0.7% on placebo vs 4.1 +/- 0.7% on PE, p > 0.4). Variation in FMD was not correlated with change in plasma isoflavone concentration (r = -0.09, p > 0.7), Glyceryl trinitrate endothelium-independent dilation was not significantly changed with PE (15.9 +/- 1.3% vs 13.7 +/- 1.2%, p > 0.1). These results fail to show a significant impact of medium-term supplementation with 80 mg/day of isoflavones on lipid and lipoprotein levels or on endothelial function in healthy, postmenopausal women. (C) 2000 by Excerpta Medica, Inc.

关键词：更年期/药物作用交叉研究双盲法内皮血管/药物作用雌激素类非甾类/药理学异黄酮类脂类/血液脂蛋白类/血液植物雌激素类植物制剂绝经后期/药物作用血管舒张/药物作用老年人女(雌)性人类中年人

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A PHARMACOLOGICAL PROFILE OF THE ENDOTHELIUM-DERIVED RELAXANT FACTOR RELEASED BY CALCITONIN GENE RELATED PEPTIDE IN RAT AORTA

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES 1992年第1期657卷 517-518页

作者： GRAY, DW MARSHALL, I Department of Pharmacology University College London London WCIE 6BT United Kingdom

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Lipopolysaccharide activates matrix metalloproteinase-2 in endothelial cells through an NF-κB-dependent pathway

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2000年第2期269卷 401-405页

作者： Kim, HG Koh, GY Chonnam Natl Univ Sch Med Natl Creat Res Initiat Ctr Cardiac Regenerat Chonju 560180 South Korea Chonnam Natl Univ Sch Med Inst Cardiovasc Res Chonju 560180 South Korea

Vascular endothelial cells release proteinases that degrade the extracellular matrix, thus enabling cell migration during angiogenesis and vasculogenesis. Endothelial cells secrete mainly the preform of matrix metalloproteinase-2 (proMMP-2). In this report, we examined several growth factors, cytokines, and other molecules for activation of MMP-2 by human umbilical vein endothelial cells. Of these factors, we found that lipopolysaccharide (LPS) is the strongest activator of MMP-2. LPS induced MMP-2 activation in a time- and dose-dependent manner. While pretreatment with zinc chelators or nuclear factor kappa B (NF-kappa B) inhibitors suppressed LPS-induced MMP-2 activation, pretreatment with phosphatidylinositol S'-kinase inhibitors had no effect. These results indicate that, in endothelial cells, LPS can directly enhance angiogenesis by inducing MMP-2 activation mediated through an NF-kappa B pathway, (C) 2000 Academic Press.

关键词： 1-磷脂酰肌醇3-激酶/拮抗剂和抑制剂细胞培养的剂量效应关系药物内皮血管/细胞学内皮血管/药物作用内皮血管/酶学酶激活脂多糖类/药理学基质金属蛋白酶2/代谢 NF-κB/代谢新生血管化病理性人类

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Tetrahydrobiopterin restores endothelial function in long-term smokers

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第1期35卷 71-75页

作者： Ueda, S Matsuoka, H Miyazaki, H Usui, MU Okuda, S Imaizumi, T Kurume Univ Sch Med Dept Internal Med 3 Kurume Fukuoka 8300011 Japan Kurume Univ Sch Med Cardiovasc Res Inst Kurume Fukuoka 8300011 Japan

OBJECTIVES We sought to test whether tetrahydrobiopterin (BH4) supplementation improves nitric oxide (NO) bioactivity in smokers. BACKGROUND In smokers, endothelium-derived NO bioactivity is impaired. BH4 is an essential cofactor of NO synthase, and its deficiency decreases NO bioactivity. METHODS Sapropterin hydrochloride, an active analogue of BH4 (2 mg/kg body weight), was administered orally to healthy male smokers and age-matched nonsmokers. Before and 3 and 24 h after sapropterin, we measured plasma levels of BH4 and examined flow-mediated vasodilation (FMV) of the brachial artery by high resolution ultrasonography, a noninvasive test of endothelial function. RESULTS Basal plasma levels of BH4 were not different between smokers and nonsmokers. Sapropterin administration increased plasma levels of BH4 by threefold at 3 h, which returned to the baseline at 24 h. Before sapropterin, FMV was significantly smaller in smokers (p = 0.0002). Sapropterin significantly augmented endothelium-dependent vasodilation in smokers, but did not affect it in nonsmokers (p = 0.001 by analysis of variance [ANOVA]). Coadministration of N-G-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor (20 mu mol), into the brachial artery completely abolished the vasodilatory effects of sapropterin (p = 0.002 by ANOVA). Endothelium-independent vasodilation by glyceryl trinitrate was between smokers and nonsmokers and was not altered by BH4. CONCLUSIONS We demonstrated that BH4 supplementation improved bioactivity of endothelium-derived NO in smokers. These observations strongly suggest that decreased NO-dependent vasodilation in smokers could be related to reduced bioactivity of BH4. (C) 1999 by the American College of Cardiology.

关键词：投药口服抗氧化剂/投药和剂量抗氧化剂/代谢生物蝶呤/投药和剂量生物蝶呤/类似物和衍生物生物蝶呤/血液肱动脉/药物作用肱动脉/生理学内皮血管/药物作用内皮血管/病理生理学一氧化氮/生理学吸烟/病理生理学血管舒张/药物作用血管舒张/生理学成年人人类男(雄)性

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IMMUNOELECTRON MICROSCOPIC LOCALIZATION OF TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR IN THE EXTRACELLULAR-MATRIX OF TRANSFORMING GROWTH FACTOR-BETA-ACTIVATED ENDOTHELIAL-CELLS

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1992年第1期667卷 46-49页

作者： PODOR, TJ LOSKUTOFF, DJ MCMASTER UNIV DEPT PATHOL HAMILTON L8N 3Z5 ONTARIO CANADA SCRIPPS RES INST COMM VASC BIOL LA JOLLA CA 92037 USA

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Sialyl Lewis^x oligosaccharide preserves myocardial and endothelial function during cardioplegic ischemia

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ANNALS OF THORACIC SURGERY 2000年第3期70卷 890-894页

作者： Schermerhorn, ML Nelson, DP Blume, ED Phillips, L Mayer, JE Harvard Univ Sch Med Childrens Hosp Dept Cardiac Surg Boston MA 02115 USA Harvard Univ Sch Med Childrens Hosp Dept Cardiol Boston MA 02115 USA Cytel Corp San Diego CA 92121 USA

Background. Neutrophil adhesion to endothelium contributes to myocardial reperfusion injury after cardiac operation. Initial neutrophil-endothelial interactions involve selectins, which bind Sialyl-Lewis(X) on neutrophils. Blockade of selectin-mediated neutrophil-endothelial interactions with CY-1503, a synthetic analogue of Sialyl-Lewis(X), might reduce reperfusion injury after myocardial ischemia. Methods. The efficacy of CY-1503 to attenuate global myocardial reperfusion injury was assessed in isolated blood-perfused neonatal lamb hearts that had 2 hours of cold cardioplegic ischemia. CY-1503 (40 mg/L) or saline vehicle was added to blood perfusate before ischemia. Contractile function (developed pressure, dP/dt) and coronary vascular endothelial function (acetylcholine response) were assessed at base line and during reperfusion. Myocardial neutrophil accumulation was assessed by myeloperoxidase quantification. Results. Compared to controls, treatment with CY-1503 improved recovery of all indices of contractile function, preserved coronary vascular endothelial function, and reduced myocardial neutrophil accumulation. Conclusions. In isolated neonatal lamb hearts that underwent hypothermic cardioplegic ischemia, CY-1503 administration reduced myocardial neutrophil accumulation and preserved endothelial and contractile function. Selectin blockade of leukocyte-endothelial interactions might attenuate reperfusion injury and enhance myocardial protection during cardiac surgical procedures. (Ann Thorac Surg 2000;70:890-4) (C) 2000 by The Society of Thoracic Surgeons.

关键词：动物新生内皮血管/药物作用内皮血管/生理学心脏/药物作用心脏/生理学 Lewis血型系统心肌收缩/药物作用心肌再灌注损伤/预防和控制中性白细胞/细胞学寡糖类/药理学寡糖类/治疗应用过氧化物酶/分析绵羊血管舒张/药物作用动物

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Tamoxifen acutely relaxes coronary arteries by an endothelium-, nitric oxide-, and estrogen receptor-dependent mechanism

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期295卷 519-523页

作者： Figtree, GA Webb, CM Collins, P Univ London Imperial Coll Sci Technol & Med Sch Med Natl Heart & Lung Inst London SW3 6LY England

In epidemiological studies tamoxifen has been associated with a reduction in the incidence of fatal myocardial infarction in women. However, the effects of tamoxifen on coronary artery reactivity are unknown. We hypothesized that tamoxifen would relax precontracted isolated rabbit coronary arteries. Rings of coronary artery from adult male and nonpregnant female New Zealand White rabbits were suspended in organ baths containing Krebs' solution;isometric tension was measured. Tamoxifen (0.1-100 muM) induced significant endothelium-dependent relaxation in precontracted rabbit coronary arteries. This relaxation was inhibited by N-omega-nitro-L-arginine methyl ester and the estrogen receptor antagonist ICI 182,780. There was no significant effect on calcium concentration-dependent contraction curves. These data suggest that tamoxifen has beneficial effects on coronary reactivity that could, at least in part, account for the reduction in risk of fatal myocardial infarction in women taking tamoxifen.

关键词：钡化合物/药理学钙通道阻滞药/药理学氯化物/药理学冠状血管/药物作用冠状血管/生理学剂量效应关系药物内皮血管/药物作用内皮血管/生理学雌二醇/类似物和衍生物雌二醇/药理学雌激素拮抗剂/药理学肌收缩/药物作用肌平滑血管/药物作用肌平滑血管/生理学 NG-硝基精氨酸甲酯/药理学一氧化氮/生理学受体雌激素/生理学选择性雌激素受体调节剂/药理学他莫昔芬/药理学血管舒张/药物作用动物女(雌)性男(雄)性兔

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