Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of high cholesterol diet (0.5% and 1%) on the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)] in the aortic tissue of rabbits were investigated in the absence or presence of probucol (0.5 gm/kg daily, orally). Five groups of ten rabbits each were studied. Group I, regular rabbit chow diet; Group II, chow + 0.5% cholesterol; Group III, chow + 0.5% cholesterol+probucol; Group IV, chow + 1% cholesterol and Group V, chow + 1% cholesterol+probucol. The aorta was removed at the end of 4 months for measurement of the antioxidant enzymes. An increase in activity of aortic antioxidant enzymes was noted in cholesterol-fed rabbits (Groups II and IV), being similar for SOD and catalase but higher for GSH-Px in Group IV as compared to Group II. Probucol was ineffective in altering this cholesterol-induced increase in enzyme activity except in Group III where it increased the activity of GSH-Px. These results suggest that aortic antioxidant enzymes are affected in hypercholesterolemia and that probucol is ineffective in altering the aortic antioxidant enzyme activity except GSH-Px activity which increased in 0.5% cholesterol-fed rabbits. The protective effects of probucol against hypercholesterolemic atherosclerosis may be partly due to an increase in the GSH-Px activity at low levels of hypercholesterolemia. At higher levels of hypercholesterolemia, the protective effects of probucol could be due to its antioxidant activity.
 ...
PMID:Effects of probucol on hypercholesterolemia-induced changes in antioxidant enzymes. 856 23

Central nervous system has a low antioxidative capacity, which is formed mainly by ascorbic acid. Therefore the cerebral tissue is threatened by the increased formation of free radicals and their metabolites (ROS--reactive oxygen species). ROS are formed such as in reperfusion phase after ischemia and in catecholamine metabolism, in oxidative stress due to hyperglycaemia. Polyunsaturated fatty acids (PUFA) are peroxidased by ROS; proteins and DNK are damaged as well. Free radicals are involved in etiology and pathogenesis of many CNS diseases, such as neuritis, Alzheimer disease, Parkinson disease, Huntington disease, aging and atherosclerosis of the brain, epilepsy, etc. During the antioxidant therapy it is necessary to consider the types of ROS, their origin and their mode of action, whether to administer hydrophilic or lipophilic antioxidants, eventually chelate agents, etc. Hydrophylic antioxidants are acting very soon after the administration, whereas the lipophilic ones reach their target tissues with a great delay. Therefore it is better to apply them preferentially like a prevention, if possible. Enzymatic antioxidants (SOD, GSPHx and catalase and others) are usually acting only for a short time. The methods of estimation of free radicals attacks are discussed as well their possible pathophysiological effects.
 ...
PMID:[Free radicals in the central nervous system]. 866 12

Reocclusion following thrombolysis is a major limitation of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) because denuded vessel wall exposed to blood following thrombolysis is a favourable surface for platelet and leucocyte deposition. We have applied a chemiluminescence technique to detect superoxide radical (0(-2)) produced by leucocytes adherent to the femoral artery 24 h after photochemically induced thrombogenesis in the guinea pig in vivo and subsequent thrombolysis by rt-PA. Intravenous administration of MCLA, a specific chemiluminescence reagent for detecting O(-2), markedly increased photon emission. the photon emission was markedly potentiated by phorbol myristate acetate and was suppressed by superoxide dismutase. Reocclusion 24 h after rt-PA induced thrombolysis was observed in 10 of 16 animals. Histological observations revealed extensive polymorphonuclear leucocytes adherent to the vessel wall at the site of thrombogenesis and thrombolysis. A higher level of 0(-2) could be detected from the arteries in which thrombolysis was induced compared with those without thrombolysis. Further, the level 0(-2) detected was greater in reoccluded arteries compared with those in which reflow was established. These observations suggest that 0(-2) is produced by adherent leucocytes at the site of thrombolysis and that leucocytes are involved in reocclusion after thrombolysis.
Atherosclerosis 1996 May
PMID:A chemiluminescent detection of superoxide radical produced by adherent leucocytes to the subendothelium following thrombolysis: studies with a photochemically induced thrombosis model in the guinea pig femoral artery. 876 84

Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.
 ...
PMID:Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery. 877 Aug 60

Heart and red blood cell endogenous antioxidant status and plasma lipids were investigated in hypertensive, 14-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Specific heart and red blood cell antioxidant enzyme activities, as well as the susceptibility of tissues to H2O2-induced glutathione (GSH) depletion and lipid peroxidation, were measured. Systolic blood pressure in SHR was greater than in WKY rats at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg (1 mmHg = 133.3 Pa); p < or = 0.05), confirming the presence of hypertension in SHR. Red blood cell catalase (CAT) and superoxide dismutase (SOD) activities were greater (p < or = 0.05) in SHR than WKY rats. Red blood cell CAT activity was positively correlated (r = +0.634; p = 0.026) with SOD, which in turn was correlated (r = +0.709; p = 0.049) with systolic blood pressure. Heart SOD activity was higher (p < or = 0.05) in SHR, while glutathione reductase (GSSG-Red) activity was lower (p < or = 0.05) than in WKY rats. This reduced ability to recycle GSH in the heart coincided with greater (p < or = 0.05) levels of H2O2-induced lipid oxidation products in SHR. Plasma total cholesterol and triacylglycerol levels were lower (p < or = 0.05) in SHR than WKY rats, with no visible signs of atherosclerosis in either SHR or WKY rats. In summary, hypertension in SHR was associated with alterations in antioxidant enzyme profiles of red blood cells and heart, with the latter showing an increased susceptibility to in vitro lipid oxidation. Although hypertension is a recognized factor in the development of human atherosclerosis, spontaneously hypertensive rats did not exhibit signs of aortic plaque, reflecting the resistance of this species to the development of atherosclerosis.
 ...
PMID:Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normotensive Wistar-Kyoto rat. 877 9

Oxy-free radicals may be involved in the pathogenesis of accelerated atherosclerosis in hypertension. We evaluated the direct antioxidant potential of probucol in hypertensive arteries by studying the spatial immunohistochemical distribution of three primary antioxidant enzymes (AEs). Nineteen normocholesterolemic New Zealand White rabbits were divided into two groups: normotensive controls (NT; n = 6) and 13 animals rendered hypertensive by surgical coarctation of abdominal aorta. The hypertensive group was subdivided into hypertensive alone (HT; n = 8) and hypertensive treated with 1% probucol (PO) for 9 weeks (HT-P; n = 5). Blood pressure rose significantly in both hypertensive groups (P < .005). At autopsy, both hypertensive groups showed similarly significant increases in mean arterial intima-media thickness (IMT) whether or not they were treated with probucol. However, only HT rabbits revealed significant increases in the intima-media depth penetration of glutathione peroxidase, superoxide dismutase, and catalase AEs. By contrast, in HT-P animals probucol produced significant reductions of immunostaining of all three AEs compared to the HT group (P < .05). Additionally, specific macrophage immunostaining revealed that the arterial wall of HT rabbits had numerous (10 to 12 per high power field) subintimal and medial macrophages as compared to the HT-P animals (1 to 2 per high power field). The blood pressure level correlated significantly with IMT in all three groups, but with depth penetration of the three AEs only in the NT and HT groups. Probucol, therefore, appears to act in concert with the native arterial antioxidant enzymes as a potent free radical scavenger to reduce oxidative stress and thus attenuate the macrophage invasive response in hypertensive arteries.
 ...
PMID:Probucol suppresses oxidant stress in hypertensive arteries. Immunohistochemical evidence. 878 83

We have investigated possible mechanisms by which n-3 fatty acid-enriched macrophages enhance the oxidation of low density lipoprotein (LDL), and the ability of antioxidant vitamins to prevent this. Macrophages were enriched with n-3 fatty acids (eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid) following incubation with fish oil. These macrophages produced large amount of TBARS in medium containing metals, and showed enhanced capacity to oxidize LDL (3-4 fold increase compared to control cells) and to accumulate the modified LDL. 5,8,11,14-eicosatetraynoic acid (ETYA, 15-lipoxygenase inhibitor) and superoxide dismutase (SOD) did not inhibit the enhanced capacity of n-3 fatty acid-enriched cells to oxidize LDL. However antioxidants, (vitamin E-enriched macrophages or vitamin C in the medium), inhibited this enhanced capacity. Medium conditioned by n-3 fatty acid-enriched cells had pro-oxidant effects on metal-initiated LDL oxidation. We conclude that n-3 fatty acid-enriched macrophages display increased oxidant capacity which is not inhibited by ETYA or SOD, and that antioxidant vitamins inhibit the enhanced capacity to oxidize LDL.
Atherosclerosis 1996 Aug 02
PMID:Enhanced capacity of n-3 fatty acid-enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins. 883 Sep 29

The goal of the present study was to determine whether oxygen-derived free radicals contribute to baroreceptor dysfunction in atherosclerosis. Baroreceptor activity was measured from the carotid sinus nerve during pressure ramps in isolated carotid sinuses of anesthetized rabbits. Rabbits fed a 0.5% to 1.0% cholesterol diet for 7.9 +/- 0.4 months (mean +/- SE; range, 5.5 to 10) developed atherosclerotic lesions in the carotid sinuses. Maximum baroreceptor activity measured at 140 mm Hg and the slope of the pressure-activity curve were reduced in atherosclerotic (n = 15) compared with normal (n = 13) rabbits (425 +/- 34 versus 721 +/- 30 spikes per second and 6.2 +/- 0.6 versus 10.8 +/- 0.8 spikes per second per mm Hg, respectively, P < .05). The level of activity was inversely related to plasma cholesterol concentration (r = .86, P < .001) and total cholesterol load (plasma concentration x duration of diet, r = .92). Mean arterial pressure was normal in both groups. Exposure of the carotid sinus to the free-radical scavengers superoxide dismutase (SOD) and catalase significantly increased maximum baroreceptor activity by 25 +/- 4% in atherosclerotic rabbits (n = 6) but caused only small and irreversible changes in activity in normal rabbits (n = 8). Catalase alone but not SOD also increased baroreceptor activity in atherosclerotic rabbits (n = 7). Exposure of the carotid sinus of normal rabbits to exogenous free radicals generated from the reaction between xanthine and xanthine oxidase inhibited baroreceptor activity in a dose-dependent and reversible manner (n = 8, P < .05). The inhibition of activity was attenuated by SOD and catalase but was not attenuated by the inhibitor of hydroxyl radical formation, deferoxamine. Neither restoration of baroreceptor activity in atherosclerotic rabbits by catalase nor inhibition of activity by xanthine/xanthine oxidase could be explained by changes in the carotid pressure-diameter relation or prostacyclin formation. These results indicate that oxidant stress inhibits baroreceptor activity and that endogenous oxyradicals produced in atherosclerotic carotid sinuses contribute to baroreceptor dysfunction.
 ...
PMID:Oxygen-derived free radicals contribute to baroreceptor dysfunction in atherosclerotic rabbits. 883 4

Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer in smokers. Lipid peroxidation is a process associated with the pathogenesis of atherosclerosis and the level of lipid peroxides is increased in smokers. In rats fed a high-fat diet, the tissue concentration of lipid peroxides was found to be increased. On nicotine administration along with a high-fat diet an additive effect was observed in lipid peroxidation and free radical scavengers. The activities of scavenging enzymes superoxide dismutase, catalase and glutathione reductase were found to be decreased, while the glutathione concentration and activity of glutathione peroxidase were enhanced.
 ...
PMID:Effect of nicotine on antioxidant defence mechanisms in rats fed a high-fat diet. 884 84

Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is one of the major toxic components of cigarette smoke that is believed to be partly responsible for the deleterious effect of cigarette smoke. Alcohol intake is another major risk factor for the development of cardiovascular disease. Lipid peroxidation is a process associated with the pathogenesis of atherosclerosis. The concentration of lipid peroxides is found to be increased in alcohol-treated rats. On nicotine administration along with alcohol, an additive effect was observed in lipid peroxidation and the antioxidant defence mechanism. The activity of scavenging enzymes superoxide dismutase, catalase and glutathione reductase was found to be decreased, while the activity of glutathione peroxidase and the concentration of glutathione were increased.
 ...
PMID:Additive effect of alcohol and nicotine on lipid peroxidation and antioxidant defence mechanism in rats. 885 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>