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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are increasing evidences that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders including hypertension. Docosahexaenoic acid (DHA) may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study was to clarify the in vitro effect of DHA on vascular smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca+2 dynamics which involves in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on the cell growth, and cell hypertrophy induced by angiotensin II as measured by flow cytometer. DHA did not have a significant effect on interleukin-1 beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in the intracellular Ca2+ concentration induced by 5-hydroxytryptamine, angiotensin II, depolarizing concentration of KCl, but not by thapsigargin. This suppression seems to be due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results suggest that DHA specifically suppresses receptor-mediated Ca2+ influx in smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.
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PMID:[Specific modulation of vascular smooth muscle cell functions by docosahexaenoic acid]. 950 27

There is increasing evidence that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders, including hypertension. Docosahexaenoic acid (DHA), may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study is to clarify the in vitro effect of DHA on cultured smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca2+ metabolism, which are involved in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on cell growth or on cell hypertrophy induced by angiotensin II as measured by flow cytometry. DHA had no stimulatory effect on interleukin-1beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP, but rather slightly inhibited it. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in intracellular Ca2+ concentration induced by angiotensin II, but not by thapsigargin. This was due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results indicate that DHA specifically suppresses Ca2+ mobilization into smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.
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PMID:Effect of docosahexaenoic acid on smooth muscle cell functions. 958 58

In the present in vitro and in vivo study we investigated the pro-oxidant effects of hemoglobin, as well as the antioxidant effects of its metabolites, in the brain. Incubation of rat brain homogenates with hemoglobin (0-10 microM) but not hemin induced lipid peroxidation up to 24 h (EC50 = 1.2 microM). Hemoglobin's effects were similar to ferrous ion (EC50 = 1.7 microM) and were blocked by the chelating agent deferoxamine (IC50 0.5 microM) and a nitric oxide-releasing compound S-nitrosoglutathione (IC50 = 40 microM). However, metabolites of hemoglobin - biliverdin and bilirubin - inhibited brain lipid peroxidation induced by cell disruption and hemoglobin (biliverdin IC50 = 12-30 and bilirubin IC50 = 75-170 microM). Biliverdin's antioxidative effects in spontaneous and iron-evoked lipid peroxidation were further augmented by manganese (2 microM) since manganese is an antioxidative transition metal and conjugates with bile pigments. Intrastriatal infusion of hemoglobin (0-24 nmol) produced slight, but significant 20-22% decreases in striatal dopamine levels. Whereas, intrastriatal infusion of ferrous citrate (0-24 nmol) dose-dependently induced a greater 66% depletion of striatal dopamine which was preceded by an acute increase of lipid peroxidation. In conclusion, contrary to the in vitro results hemoglobin is far less neurotoxic than ferrous ions in the brain. It is speculated that hemoglobin may be partially detoxified by heme oxygenase and biliverdin reductase to its antioxidative metabolites in the brain. However, in head trauma and stroke, massive bleeding could significantly produce iron-mediated oxidative stress and neurodegeneration which could be minimized by endogenous antioxidants such as biliverdin, bilirubin, manganese and S-nitrosoglutathione.
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PMID:Hemoglobin and iron-evoked oxidative stress in the brain: protection by bile pigments, manganese and S-nitrosoglutathione. 1063 Jun 86

The importance of nutrition in protecting the living organism against the potentially lethal effects of reactive oxygen species and toxic environmental chemicals has recently been realized. This new perspective has prompted re-evaluation of the food constituents of human diet from the point of view of their nutritional adequacy, deficiency and toxicity. The biological antioxidant defense system is an integrated array of enzymes, antioxidants and free radical scavengers. These include glutathione reductase, glutathione-s-transferase, glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, superoxide dismutase (SOD) and catalase, together with the antioxidant vitamins C, E and A. The individual components of this system get utilized in various physiological process and for chemoprotection and therefore require replenishment from the diet. Other components of the diet like carbohydrates, proteins and lipids are important for maintaining the levels of various enzymes required in body's defense system providing protection against carcinogens. However, the emerging newer concepts focus on the role of trace elements and other dietary components in antioxidant defense and detoxification mechanisms. Trace elements like Iron, zinc magnesium, selenium, copper, and manganese are some of the elements involved in antioxidant defense mechanisms. Inadequate intake of these nutrients has been associated with ischemic heart disease, arthritis, stroke and cancer, where pathogenic role of free radicals is suggested. Further the importance of diet in the prevention of chemical induced toxicity can not be undetermined. Recent reports on the role of bioflavonoids as antioxidents and their potential use to reduce the risks of coronary heart disease and cancer in human beings have opened a new arena for future research. Induction of the cytochrome P450 isoenzymes by food pyrolysis, mutagens, alcohol and fasting, on the other hand is reported to contribute to chemical toxicity and carcinogenecity. Certain chemicals moieties in the food are mutagenic and carcinogenic.
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PMID:Role of nutrition in toxic injury. 1064 Nov 28

Free radical are highly reactive chemical species with an unpaired electron in an atomic or molecular orbital. In biological systems, the most important free radicals are superoxide anion and hydrogen peroxide; in the presence of transition metals such as iron, copper and manganese both these free radicals produce hydroxyl radicals. Free radicals attack proteins, nuclei acids and membranes containing large quantities of polyunsaturated fatty acids. Because of their toxicity, the organism has developed ways to deactivate them. The superoxide dismutase enzyme (SOD) catalyzes dismutation of the superoxide radical into hydrogen peroxide and oxygen hydrogen peroxide is in turn reduced to water and oxygen by peroxidase glutathione and catalase enzymes. The production of radicals in the brain is due to catecholamine metabolism such as dopamine and norepinephrine and is increased by the presence of transition metals and by a deficiency of antioxidant agents such as vitamin E. Two main groups of dementia exist in older age: the multi-infarctual dementias, caused by cerebrovascular disorders and the primary degenerative disorders such as Alzheimer, where no vascular disease is evident. Free radicals play an important role in Parkinson's disease, in Alzheimer's disease and in stroke. The value of SOD and CAT activity following the above mentioned degenerative diseases differ among the various studies carried out. In Alzheimer's disease, the value of SOD activity probably increases in the neuropathologically involved areas. In stroke, the SOD value does not vary either in the ischemic area or in the peri-infarctual one during the first 24 hrs after lesion, while the CAT value decreases.
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PMID:Free radicals: important cause of pathologies refer to ageing. 1070 16

Manganese-salen complexes (Mn-Salen), including EUK-8 [manganese N,N'-bis(salicylidene)ethylenediamine chloride] and EUK-134 [manganese 3-methoxy N,N'-bis(salicylidene)ethylenediamine chloride], have been reported to possess combined superoxide dismutase (SOD) and catalase mimetic functions. Because of this SOD/catalase mimicry, EUK-8 and EUK-134 have been investigated as possible therapeutic agents in neurological disorders resulting from oxidative stress, including Alzheimer's disease, Parkinson's disease, stroke and multiple sclerosis. These actions have been explained by the ability of the Mn-Salen to remove deleterious superoxide (O(2)(-)) and H(2)O(2). However, in addition to oxidative stress, cells in models for neurodegenerative diseases may also be subjected to damage from reactive nitrogen oxides (nitrosative stress), resulting from elevated levels of NO and sister compounds, including peroxynitrite (ONOO(-)). We have been examining the interaction of EUK-8 and EUK-134 with NO and ONOO(-). We find that in the presence of a per-species (H(2)O(2), ONOO(-), peracetate and persulphate), the Mn-Salen complexes are oxidized to the corresponding oxo-species (oxoMn-Salen). OxoMn-Salens are potent oxidants, and we demonstrate that they can rapidly oxidize NO to NO(2) and also oxidize nitrite (NO(2)(-) to nitrate (NO(2)(-)). Thus these Mn-Salens have the potential to ameliorate cellular damage caused by both oxidative and nitrosative stresses, by the catalytic breakdown of O(2)(-), H(2)O(2), ONOO(-) and NO to benign species: O(2), H(2)O, NO(2)(-) and NO(3)(-).
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PMID:Oxidation of nitric oxide by oxomanganese-salen complexes: a new mechanism for cellular protection by superoxide dismutase/catalase mimetics. 1199 46

Synthetic catalytic scavengers of reactive oxygen species (ROS) may have broad clinical applicability. In previous papers, two salen-manganese complexes, EUK-8 and EUK-134, had superoxide dismutase (SOD) and catalase activities and prevented ROS-associated tissue injury. This study describes two series of salen-manganese complexes, comparing catalytic ROS scavenging properties and cytoprotective activities. The compounds vary widely in ability to scavenge hydrogen peroxide, with this activity most influenced by salen ring alkoxy substitution and aromatic bridge modifications. In contrast, all compounds show comparable SOD activities. The most active alkoxy-substituted catalase mimetics protected cultured cells from hydrogen peroxide, and a subset of these were also neuroprotective in a rodent stroke model. Thus, structural modification of the prototype EUK-8 yields compounds with enhanced catalase activity and, in turn, biological effectiveness. This supports the concept that salen-manganese complexes represent a class of SOD and, in particular, catalase mimetics potentially useful against ROS-associated diseases.
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PMID:Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and cytoprotective agents: structure-activity relationship studies. 1223 34

The effects of motorcycle exhaust particulate on vasoconstriction were determined using rat thoracic aortas under organ culture conditions treated with organic extracts of motorcycle exhaust particulate from a two-stroke engine. The motorcycle exhaust particulate extract (MEPE) induced a concentration-dependent enhancement of vasoconstriction elicited by phenylephrine in the organ cultures of both intact and endothelium-denuded aortas for 18 h. Nifedipine (an L-type Ca2+ channel blocker), manganese acetate (an inorganic Ca2+ channel blocker), and staurosporine (a nonselective protein kinase C inhibitor), but not the selective protein kinase C inhibitor chelerythrine, inhibited the enhancement of vasoconstriction by MEPE. Staurosporine has also been reported as a myosin light chain kinase (MLCK) inhibitor, so we tested whether the MLCK pathway was involved in the effect of MEPE. The results showed that ML-9 (a selective MLCK inhibitor) could inhibit the enhancement of vasoconstriction by MEPE. The phosphorylation of a 20-kDa myosin light chain in a primary culture of rat vascular smooth muscle cells was also enhanced by MEPE. Moreover, we also examined the role of reactive oxygen species (ROS) in the stimulatory effect of MEPE on vasoconstriction. The antioxidant N-acetylcysteine significantly inhibited the enhancement of vasoconstriction by MEPE. A time-dependent increase in ROS production by MEPE was also detected in primary cultures of vascular smooth muscle cells. These results indicate that MEPE induces a marked enhancement of vasoconstriction in aortas under organ culture conditions and imply that a ROS-Ca2+-MLCK pathway may be involved in this MEPE-induced response.
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PMID:Motorcycle exhaust particulates enhance vasoconstriction in organ culture of rat aortas and involve reactive oxygen species. 1280 40

Manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), which has been known as a cell permeable superoxide dismutase mimetic, induced concentration-dependent contraction in rat carotid artery acting directly on smooth muscle. The contractile action was more prominent in the preparation from stroke-prone spontaneously hypertensive rats (SHRSP) compared with that from Wistar Kyoto rats (WKY). It was abolished by the removal of extracellular Ca(2+) or the application of verapamil. These results suggest that the MnTMPyP-induced contraction is brought about by Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCC) and that the difference in VDCC is the cause of the difference in MnTMPyP action between preparations from WKY and SHRSP.
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PMID:Contraction of arterial smooth muscle of normotensive and spontaneously hypertensive rats by manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP). 1283 46

Statins inhibit cholesterol biosynthesis and protect against ischaemic stroke. It has become increasingly apparent that the beneficial effects of statin therapy may extend beyond lowering of serum cholesterol. The present study was done to explore possible pleiotropic statin effects at the level of the cerebral vascular smooth muscle. Lovastatin, lovastatin acid, simvastatin and pravastatin, were added to segments of the rat basilar artery and effects on contraction and Ca2+ handling were examined. Pravastatin had no effect on contraction. Simvastatin, lovastatin, and, to a lesser degree, lovastatin acid, caused relaxation (IC50=0.8, 1.9 and 22 micromol/l) of both intact and denuded arteries precontracted with 5-HT or high-K+. This effect was not reversed by mevalonate, suggesting that it was not related to cholesterol or isoprenoid metabolism. Relaxation was associated with a reduction of the intracellular Ca2+ concentration measured with Fura 2 and with a reduced Mn2+ quench rate, suggesting a direct effect on ion channels in the smooth muscle cell membrane. Current measurements in isolated and voltage clamped basilar artery muscle cells demonstrated that both lovastatin and lovastatin acid inhibit L-type Ca2+ current. We propose that lipophilicity is an important factor behind the effects of statins on vascular tone and that Ca2+ current inhibition is the likely mechanism of action.
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PMID:Lovastatin induces relaxation and inhibits L-type Ca(2+) current in the rat basilar artery. 1296 37


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