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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both atherosclerotic lesions and hypoxia alter the contractile properties of the arterial wall and, in particular, may interfere with the relaxation mechanisms dependent or not on the endothelium. The present study was designed to test the effect of severe hypoxia on the contractile behavior of the atherosclerotic rabbit aorta. Segments of aortas obtained from control, cholesterol-fed, or Watanabe hereditary hyperlipidemic rabbits were mounted in organ chambers for isometric tension recording. A change of the bath PO2 from "normoxic" conditions (95% O2-5% CO2) to "hypoxic" conditions (95% N2-5% CO2) caused relaxation in the precontracted control aortas (by approximately 85%) but a transient contraction (approximately 20% of the maximal contraction obtained with 30 mM KCl) followed by a relaxation in the precontracted atherosclerotic aortas. Both types of responses were observed in aortas contracted with aggregating platelets, 5-hydroxytryptamine (5-HT), norepinephrine, endothelin, and prostaglandin F2 alpha. The hypoxic contractions in atherosclerosis were not dependent on the presence of an intact endothelium. They could not be antagonized by blockers of alpha-adrenoceptors, 5-HT2 receptors, histamine receptors, thromboxane receptors, and muscarinic cholinoreceptors. Inhibitors of cyclooxygenase, lipoxygenase, Na+, K(+)-ATPase, and free radical scavengers or an activator of endothelium-derived relaxing factor did not significantly affect the hypoxic contraction; the absence of effect of some inhibitors of protein synthesis seems to rule out the involvement of endothelin, angiotensin II, and bradykinin. The hypoxic contraction was not influenced by omission of Ca2+ from the medium or by inhibition of Ca2+ influx but was prevented by blockade of intracellular Ca2+. The inhibitor of nitric oxide synthase (nitro-L-arginine, 100 microM) and the guanylyl cyclase inhibitor (methylene blue, 10 microM) both enhanced the initial contractile responses to 5-HT to a similar extent as hypoxia and completely prevented the hypoxic contraction in the atherosclerotic tissues. The cyclic nucleotide analogues 8-bromo-cGMP and dibutyryl cAMP also inhibited the hypoxic contraction in the atherosclerotic aorta. The cGMP levels were markedly decreased and the cAMP levels were moderately decreased in the aortas of the cholesterol-fed rabbits as compared with the control aortas. Hypoxia further decreased cGMP but not the cAMP levels in atherosclerotic aortas with and without endothelium. Our data thus demonstrate the occurrence of an unusual vasoconstrictor response in atherosclerotic arteries; this constrictor response depends on the availability of intracellular Ca2+ and seems to be due to the further inhibition of an already impaired cGMP production.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hypoxia causes an abnormal contractile response in the atherosclerotic rabbit aorta. Implication of reduced nitric oxide and cGMP production. 838 23

This paper reviews the available evidence concerning the atherogenic potential of carbon monoxide. The evidence comes from two different types of studies--epidemiology studies on populations of humans chronically exposed to carbon monoxide, and animal studies conducted under conditions of controlled exposure to carbon monoxide. Data from both epidemiology and animal studies suggest that carbon monoxide is not atherogenic. Therefore, the increased levels of atherosclerosis associated with smoking as reported in epidemiology studies of human smokers probably cannot be attributed to CO exposure.
Atherosclerosis 1993 Mar
PMID:The atherogenic potential of carbon monoxide. 850 43

We studied the relationship between postoperative brain dysfunction and the state of atherosclerosis in the patients of open heart surgery, by analyzing the intraoperative cerebral oxygen saturation (rSO2) and the CO2 reaction. The subjects were 143 patients with average age of 64 years. The patients with low postoperative Hasegawa's Dementia Score were categorized as brain dysfunction group. rSO2 was utilized to monitor cerebral blood flow, and AI and stiffness parameter beta were used for evaluation of systemic atherosclerosis. Postoperative brain dysfunction was confirmed in 12%. There were significantly high values of AI and beta as well as low rSO2, in elder age with low cardiac index and no correlation was observed between rSO2 and PaCO2 in the brain dysfunction group. The results suggested that a higher level of atherosclerosis is associated with the postoperative brain dysfunction with resultant decreased cerebral blood flow and disturbed reaction to CO2 of cerebral blood vessels.
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PMID:[Association of postoperative brain dysfunction and atherosclerosis, intraoperative rSO2 and CO2 reaction in open heart surgery]. 872 Nov 25

Hypoxia has profound effects on blood vessel tone. Acute hypoxia causes pulmonary vasoconstriction and chronic hypoxia causes smooth muscle cell replication and extracellular matrix accumulation resulting in vessel wall remodeling. The cellular responses to hypoxia involve complex cell-cell interactions mediated by the release of growth factors, cytokines and biological messengers. We have reported that hypoxia increases the expression of a number of genes encoding vascular cell mitogens produced by endothelial cells: platelet-derived growth factor B (PDGF-B); endothelin-1 (ET-1); and vascular endothelial growth factor (VEGF). A 28-bp enhancer in the 5' upstream region of the VEGF gene mediates the expression of VEGF by endothelial cells under conditions of hypoxia. Hypoxia, however, has opposite effects on the vasodilator nitric oxide (NO); hypoxia suppresses both the transcriptional rate of the endothelial nitric oxide synthase gene and the stability of its mRNA. These endothelial-dependent processes would lead to vessel wall remodeling characteristic of a number of diseases from atherosclerosis to pulmonary hypertension. The smooth muscle cell also responds to hypoxia. It increases the transcriptional rate of the heme oxygenase gene-1 responsible for the breakdown of heme to carbon monoxide (CO) and biliverdin. CO is a vasodilator with properties similar to the well-studied molecule NO. CO suppresses the production of ET-1 and PDGF-B by endothelial cells. The regulated production of NO and CO under hypoxia, therefore, results in complex feedback loop interactions leading to altered smooth muscle cell growth in an autocrine and paracrine manner.
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PMID:Mechanisms by which oxygen regulates gene expression and cell-cell interaction in the vasculature. 902 18

Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.
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PMID:The role of nicotine in smoking-related cardiovascular disease. 924 58

Oxidation of low density lipoprotein (LDL) has been recognized as playing an important role in the initiation and progression of atherosclerosis. In this study, the effects of aged garlic extract and one of its major compounds, S-allylcysteine, on oxidized LDL-induced cell injury were studied. Pulmonary artery endothelial cells were pre-incubated with the garlic extract (1, 2.5 and 5 mg mL-1) or S-allylcysteine (0.1, 1, 10 and 20 mM) at 37 degrees C and 5% CO2 for 24 h, washed, and then exposed to 0.1 mg mL-1 oxidized LDL for 24 h. Lactate dehydrogenase release as an index of membrane damage, methylthiazol tetrazolium assay for cell viability and thiobarbituric acid reactive substances indicating lipid peroxidation were determined. Preincubation of endothelial cells with the extract or S-allylcysteine significantly prevented membrane damage, loss of cell viability and lipid peroxidation. The data indicate that these compounds can protect vascular endothelial cells from injury caused by oxidized LDL, and suggest that they may be useful for prevention of atherosclerosis.
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PMID:Garlic compounds protect vascular endothelial cells from oxidized low density lipoprotein-induced injury. 930 60

Atmospheric pollution is not considered to be a factor of cardiovascular risk in the same way as passive smoking, arterial hypertension or coronary heredity. Passive smoking is now recognised as a factor of high cardiovascular death rate and must provoke public authorities to reinforce the measures to ban smoking in public places. With regard to other pollutants, carbon monoxide, by chronic hypoxia, has been incriminated in destabilisation of high risk patients--coronary or cardiac insufficiency. The responsibility of other polluting agents on cardiovascular death rate, NO2, SO2, or O3 has not been shown clearly, because many confusing factors intervene, especially in the matter of coronary atherosclerosis.
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PMID:[Urban air pollution and cardiovascular disease]. 945 37

The purpose of this study was to determine whether platelets and vascular endothelial cells would liberate nitric oxide free radical (NO)* and NO-derived oxidant species after exposure to carbon monoxide (CO) at concentrations up to 100 parts per million (ppm). We hypothesized that exposure to environmentally relevant concentrations of CO would increase production of agents that may be involved in human pathological processes, such as atherosclerosis. Platelets obtained from rats released NO when incubated with CO, but CO did not increase platelet nitric oxide synthase activity. Platelets released comparable NO levels when they were exposed to CO in vitro and when taken from rats that had been exposed to CO. Partial pressures of CO as low as 10 ppm could successfully compete with NO for intraplatelet binding sites in in vitro studies. We conclude that CO enhanced the release of NO from platelets because it inhibited NO sequestration by intraplatelet binding sites, and that this phenomenon can occur with exposure to CO concentrations found in the environment. Bovine pulmonary artery endothelial cells released NO in response to CO exposure. Carbon monoxide did not affect the transport of L-arginine across the plasma membrane or nitric oxide synthase activity; therefore, the mechanism appeared to be based on a disturbance of intracellular NO sequestration. Cells incubated with CO also released into the surrounding medium peroxynitrite, an NO-derived oxidant, based on oxidation of dihydrorhodamine 123 and p-hydroxyphenylacetic acid. Peroxynitrite-mediated oxidative stress to endothelial cells was identified as increased concentrations of nitrotyrosine in cell lysates, and by measuring the release of radioactive chromium. Carbon monoxide caused an acute injury when cells were continuously exposed for 4 hours, and a delayed injury when cells were exposed for 2 hours. Delayed injury was documented by leakage of radioactive chromium and by uptake of a vital fluorescent stain, ethidium homodimer-1, between 6 and 20 hours after CO exposure. Oxidative stress caused by CO exhibited several unique aspects because CO exposure did not alter the cellular content of reduced sulfhydryls nor did CO augment oxidative stress caused by superoxide, hydrogen peroxide, or a flux of NO. We concluded that concentrations of CO achieved in vivo when humans are exposed to CO concentrations found in the environment can cause endothelial cells to liberate NO and NO-derived oxidants, and that these products can adversely affect cell physiology.
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PMID:Mechanism of oxidative stress from low levels of carbon monoxide. 947 63

We studied cytotoxic effects (CTE) induced in confluent cultures of human umbilical vein endothelial cells (HUVEC) by initiators of free-radical reactions (FRR): H2O2 (10(-6)-10(-9) M), recombinant human tumor necrosis factor-[symbol; see text] (TNF-alpha, 0.05-100 ng/ml), and a combination of TNF-alpha with low-density lipoproteins (LDL, 100 microgram/ml). HUVEC were incubated with these substances for 6 or 24 h in parallel tests performed under aerobic (CO2-incubator) and ischemic conditions (a mixture of 95% N2 + 5% CO2 in RPMI-1640 medium containing no substrate additives, growth factor or protein). HUVEC viability was determined by counting cells adherent to the bottom of wells after 24 h of reincubation under aerobic conditions in the growth medium (Plating Efficiency Index). The data showed that: 1) CTE of these compounds were dose-dependent (H2O2 and TNF-alpha) and time-dependent (TNF-alpha); 2) CTE of FRR initiators and CTE of ischemia were synergistic, that is, their combination produced a greater decrease HUVEC viability than any substance examined or ischemia alone; 3) CTE of TNF-alpha observed in experiments in substrate-deficient, protein-free medium was considerably stronger than in the growth medium; 4) a combination of TNF-a and LDL caused a stronger CTE on HUVEC than either factor alone, and this synergism was more pronounced during incubation under ischemic conditions. Thus, the data indicate that FRR initiators and TNF-alpha + LDL particularly increase the severity of ischemic injuries of EC and therefore they can be factors which in hypercholesterolemic patiens predispose vascular wall to atherosclerosis.
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PMID:[Comparative evaluation of the cytotoxic effect of hydrogen peroxide and tumor necrosis factor alpha on nonischemic and ischemic endothelial cells]. 970 22

The roles of superoxide (O2.-), peroxynitrite, and carbon dioxide in the oxidative chemistry of nitric oxide (.NO) are reviewed. The formation of peroxynitrite from .NO and O2.- is controlled by superoxide dismutase (SOD), which can lower the concentration of superoxide ions. The concentration of CO2 in vivo is high (ca. 1 mM), and the rate constant for reaction of CO2 with -OONO is large (pH-independent k = 5.8 x 10(4) M(-l)s(-1)). Consequently, the rate of reaction of peroxynitrite with CO2 is so fast that most commonly used scavengers would need to be present at very high, near toxic levels in order to compete with peroxynitrite for CO2. Therefore, in the presence of physiological levels of bicarbonate, only a limited number of biotargets react directly with peroxynitrite. These include heme-containing proteins such as hemoglobin, peroxidases such as myeloperoxidase, seleno-proteins such as glutathione peroxidase, proteins containing zinc-thiolate centers such as the DNA-binding transcription factors, and the synthetic antioxidant ebselen. The mechanism of the reaction of CO2 with OONO produces metastable nitrating, nitrosating, and oxidizing species as intermediates. An analysis of the lifetimes of the possible intermediates and of the catalysis of peroxynitrite decompositions suggests that the reactive intermediates responsible for reactions with a variety of substrates may be the free radicals .NO2 and CO3.-. Biologically important reactions of these free radicals are, for example, the nitration of tyrosine residues. These nitrations can be pathological, but they also may play a signal transduction role, because nitration of tyrosine can modulate phosphorylation and thus control enzymatic activity. In principle, it might be possible to block the biological effects of peroxynitrite by scavenging the free radicals .NO2 and CO3.-. Because it is difficult to directly scavenge peroxynitrite because of its fast reaction with CO2, scavenging of intermediates from the peroxynitrite/CO2 reaction would provide an additional way of preventing peroxynitrite-mediated cellular effects. The biological effects of peroxynitrite also can be prevented by limiting the formation of peroxynitrite from .NO by lowering the concentration of O2.- using SOD or SOD mimics. Increased formation of peroxynitrite has been linked to Alzheimer's disease, rheumatoid arthritis, atherosclerosis, lung injury, amyotrophic lateral sclerosis, and other diseases.
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PMID:Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. 974 78


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