UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. To determine the acute effects of irradiation on the functionality of vessel, rat aortic rings were mounted in an organ bath for isometric tension measurements and irradiated (60Co, 1 Gy min(-1), 15 min). 2. Irradiation, which is without effect on non-contracted or endothelium-denuded vessels, led to an immediate and reversible increase in vascular tone on (-)-phenylephrine (1 microM)-precontracted aortic rings. The tension reached a plateau about 5 min after the beginning of irradiation. 3. The maximal radiation-induced contraction occurred on aortic rings relaxed by acetylcholine (ACh) (1 microM). In this condition, the addition of catalase (1000 u ml(-1)), which reduces hydrogen peroxide, and DMSO (0.1% v/v), which scavenges hydroxyl radical, had no influence on tension level while superoxide dismutase (SOD) (100 u ml(-1)), a superoxide anion scavenger, reduced the observed contraction. A similar result was obtained in the presence of indomethacin (10 microM), a cyclo-oxygenase blocker. 4. Pretreatment of rings with the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) (10-100 microM) inhibited the radiation-induced contraction. 5. This effect was dose rate-dependent and even occurred for a very low dose rate (0.06 Gy min(-1)). 6. The present results indicate that gamma-radiation induces an instantaneous vascular tone increase that is endothelium and dose rate-dependent. This effect is (i) maximal when nitric oxide (NO) is produced, (ii) greatly reduced by SOD and (iii) inhibited by L-NAME, suggesting a major involvement of complexes between NO and superoxide anion.
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PMID:Early effects of acute gamma-radiation on vascular arterial tone. 955 1

Local inhibition of nitric oxide (NO) synthesis with L-arginine analogs such as NG-nitro-L-arginine methyl ester (L-NAME) decreased red blood cell velocity (VRBC) in capillaries and increased leukocyte adhesion in postcapillary venules in rat skeletal muscle. The goal of the present study was to determine the mechanism of this response to L-NAME. Using intravital videomicroscopy, we examined blood flow in the surface microvasculature of rat extensor digitorum longus muscle. L-NAME (30 mM in the pipette) locally applied to capillaries (300 microns from feeding arteriole) reduced VRBC [control VRBC = 244 +/- 53 (SE) microns/s; delta VRBC = -52 +/- 8%] and increased leukocyte adhesion (from 0.2 +/- 0.01 to 1.3 +/- 0.3 cells/100 microns) in control animals. Systemic pretreatment with fucoidan (selectin binder), superoxide dismutase and catalase (extracellular antioxidants), dimethylthiourea (intracellular antioxidant), or ketotifen (mast cell stabilizer) did not alter this response. Pretreatment with CL26, an anti-CD18 antibody, abolished the L-NAME response. Our results suggest that L-NAME increased leukocyte-endothelial interactions via an effect on CD11/CD18 or its ligand, intercellular adhesion molecule.
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PMID:Local L-NAME decreases blood flow and increases leukocyte adhesion via CD18. 957 30

Previous studies from our laboratory have shown that nitric oxide (NO) can reduce the release of free radicals from activated leukocytes. The aim of this study was to assess the role of endothelium-derived nitric oxide and leukocyte-derived free radicals in the contractile response to non-preactivated leukocytes. Vessel tension studies were performed in rabbit endothelium-intact aortic vessel rings precontracted with 5-hydroxytryptamine (1 microM). Addition of leukocytes isolated from rabbit blood were added to the rings in increasing concentrations (10(3)-10(6) cell ml(-1)) under control conditions and in the presence of L-nitroarginine methyl ester (L-NAME 1 mM), D-NAME (1 mM), or superoxide dismutase (100 U ml(-1)). The responses to superoxide radical (generated by xanthine plus xanthine oxidase, X/XO), hydrogen peroxide, hypochlorite and peroxynitrite were also assessed. The nature of the free radicals released from non-activated isolated leukocytes, zymosan-stimulated leukocytes (in whole blood) and isolated vessel rings was assessed using luminol-enhanced chemiluminescence. Cumulative addition of leukocyte suspensions to aortic rings caused a concentration-dependent contractile response which was abolished by preincubation of the vessel ring with L-NAME. D-NAME and superoxide dismutase were without effect. All the free radicals tested produced a relaxation of the precontracted aortic ring. The response to X/XO was not affected by superoxide dismutase, but abolished by catalase. The responses to hydrogen peroxide and hypochlorite were both found to be dependent upon the presence of endothelium and NO. The response to peroxynitrite was endothelium-independent and was blocked by methylene blue. While the main free radical released from unstimulated leukocytes and vessel rings was superoxide, the main radical released from activated leukocytes was found to be hypochlorite. These results suggest that the vascular contraction seen in response to non-preactivated leukocytes is due to inhibition, by NO, of the release of free radicals from the leukocytes when activated by contact with the vascular endothelium, thus allowing co-released vasoconstrictor substances to exert their effect.
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PMID:Role of nitric oxide and free radicals in the contractile response to non-preactivated leukocytes. 959 26

1. Nitric oxide (NO)-mediated, endothelium-dependent vasodilator function in rat aortic smooth muscle was investigated in an in vitro model of endogenous vascular superoxide anion stress, generated by pretreatment with the Cu/Zn superoxide dismutase (SOD, EC 1.15.1.1) inhibitor, diethyldithiocarbamate (DETCA). 2. Contraction to noradrenaline (NA, 1 nM - 1 microM) in endothelium-intact vessels was augmented after a 30 min pretreatment with DETCA (10 mM) followed by 30 min washout. This effect was abolished by N(G)-nitro-L-arginine methyl ester (L-NAME, 0.3 mM) and removal of the endothelium and partially reversed by exogenous Cu/Zn SOD (200 u ml(-1)). 3. Endothelium- and basal NO-dependent vasorelaxation to the phosphodiesterase (PDE) type V inhibitor ONO- 1 505 (4-[2-(2-hydroxyethoxy)ethylamino]-2-(1H-imidazol-1-yl)-6-methoxyquin azoline methanesulphonate) (0.1-10 microM) was inhibited after DETCA (10 mM) pretreatment. In addition, the ability of L-NAME (0.3 mM) to enhance established contractile tone was effectively absent. 4. In contrast, DETCA pretreatment did not significantly affect vasorelaxation to acetylcholine (ACh, 1 nM - 3 microM) or S-nitroso-N-acetyl penicillamine (SNAP, 0.03-30 microM). However, L-NAME (0.3 mM) unmasked an inhibitory effect of DETCA pretreatment on vasorelaxation to SNAP in endothelium-intact vessels while markedly potentiating vasorelaxation to SNAP in control tissue. 5. L-NAME (0.3 mM)- and exogenous catalase (200 u ml(-1))-sensitive vasorelaxation to exogenous Cu/ Zn SOD (200 u ml(-1)) was greater after DETCA (10 mM) pretreatment in endothelium-intact aortic rings. This difference was abolished by catalase (200 u ml(-1)). 6. In conclusion, tissue Cu/Zn SOD inhibition elicited a selective lesion in basal endothelial function in rat isolated aortic smooth muscle, consistent with the inactivation of basal NO by superoxide anion. The resulting leftward shift in nitrovasodilator reactivity, due to the loss of the tonic depression by basal NO, is likely to mask the inhibitory effect of superoxide anion on agonist-stimulated endothelial function and nitrovasodilator-derived NO, thereby accounting for the differential pattern of endothelial dysfunction after DETCA pretreatment.
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PMID:Interaction between superoxide anion and nitric oxide in the regulation of vascular endothelial function. 963 Mar 65

In the present investigation involvement of endothelial-derived reactive oxygen species (ROS) and their interaction with nitric oxide (NO), during norepinephrine (NE)-induced contraction of rat aortic rings was studied. NE (1x10(-10) M to 1x10(-5) M) caused concentration-dependent contractio n of the endothelium intact aortic rings. In the presence of hydroxyl radical scavengers, histidine (1x10(-3) M), mannitol (3x10(-3) M), dimethyl sulfoxide (50x10(-3) M) or thiourea (1x10(-3) m), superoxide dismutase (superoxide radical scavenger, SOD 10 or 100 U ml-1) or catalase (hydrogen peroxide inactivator 3, 10, or 100 U ml-1) the concentration-response curve of NE was shifted towards the right. Interestingly, in NG-nitro-l-arginine methyl ester (L-NAME) (1x10(-5) M, a NO synthase inhibitor) pretreated rings, NE-induced contractions were not inhibited by SOD or extracellular hydroxyl radical scavengers (mannitol and histidine). However, in these rings NE-induced contractions were found to be attenuated by endogenous hydroxyl radical scavengers (thiourea and DMSO) or catalase. In the endothelium denuded rings no significant effect of these scavengers on NE-induced contractions was observed. These results thus indicate the involvement of endothelium-derived hydrogen peroxide, superoxide and hydroxyl radicals in the NE-induced contractions. In addition, endothelial NO interacts with the ROS generated during rat aortic ring contractions.
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PMID:Role of endothelial-derived reactive oxygen species and nitric oxide in norepinephrine-induced rat aortic ring contractions. 977 89

Thrombi have been induced by iontophoretic application of ADP on the venules of the mesentery of male Wistar rats (250-350 g). We determined the thrombus growth which is a reflection of platelet recruitment. We have demonstrated the ability of two oxygen-free radical scavengers, superoxide dismutase (SOD), a superoxide anion scavenger, and catalase, a hydrogen peroxide scavenger, to reduce thrombus growth. Imidazole, a thromboxane synthase inhibitor also reduces the thrombus growth. Dimethylthiourea, a hydroxyl radical scavenger, does not alter the thrombus size. The administration of a NO synthase inhibitor, Ng-nitro-L-arginine methyl ester (L-NAME), sharply increased the volume of the thrombus. Our results show the implication of superoxide anion, hydrogen peroxide and nitric oxide in platelet recruitment. (c) 1998 The Italian Pharmacological Society.
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PMID:Oxygen-free radicals and nitric oxide are involved in the thrombus growth produced by iontophoresis of ADP. 980 14

The present study analyses the influence of hypertension and endothelium on the effect induced by hydrogen peroxide (H2O2) on basal tone in aortic segments from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) of 6-month-old, as well as the possible mechanisms involved. Single (1 mM) or cumulative (100 nM-10 mM) concentrations of H2O2 produced a transient contraction or a concentration-dependent increase of basal tone, respectively, in segments from WKY and SHR. In both cases, the contractions were higher in intact segments from hypertensive than from normotensive rats, and increased by endothelium removal in both strains. Catalase (1000 u ml(-1), a H2O2 scavenger) abolished the contraction elicited by 1 mM H2O2 in both strains. Superoxide dismutase (SOD, 150 u ml(-1)) and dimethylsulphoxide (DMSO, 7 mM), scavengers of superoxide anions and hydroxyl radicals, respectively, did not alter H2O2-induced contractions in intact segments from both strains. However, L-NG-nitroarginine methyl ester (L-NAME, 100 microM, a nitric oxide synthase inhibitor) increased the response to H2O2 in normotensive rats, although the increase was less than that produced by endothelium removal. Incubation of segments with 1 mM H2O2 for 15 min and subsequent washout reduced the contractile responses induced by 75 mM KCl in intact segments from SHR and in endothelium-denuded segments from both strains; this effect being prevented by catalase (1000 u ml(-1)). Indomethacin (10 microM, a cyclo-oxygenase inhibitor) and SQ 29,548 (10 microM, a prostaglandin H2/thromboxane A2 receptor antagonist) practically abolished the contractions elicited by H2O2 in normotensive and hypertensive rats. We conclude that: (1) the oxidant stress induced by H2O2 produces contractions mediated by generation of a product of the cyclo-oxygenase pathway, prostaglandin H2 or more probably thromboxane A2, in normotensive and hypertensive rats; (2) oxygen-derived free radicals are not involved in the effect of H2O2; (3) in normotensive rats, endothelium protects against H2O2-mediated injury to contractile machinery, determined by the impairment of KCl-induced contractions; and (4) endothelial nitric oxide has a protective role on the contractile effect induced by H2O2, that is lost in hypertension.
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PMID:Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats. Endothelial modulation and mechanism involved. 986 64

In prostglandin F2alpha(PGF2alpha)-precontracted isolated canine basilar arterial rings, hydrogen peroxide (H2O2) produced endothelium-dependent relaxations at concentrations of from 4.4 x 10(-7) - approximately 4.4 x 10(-5) M. Removal of extracellular Ca2+ ([Ca2+]0) attenuated the relaxant effects of H2O2. Complete inhibition of H2O2 relaxant action was obtained after buffering intracellular Ca2+ ([Ca2+]i), in the endothelial cells, with 10 microM 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). The H2O2-induced relaxations could be abolished completely by 1200 u/ml catalase and was suppressed significantly by 0.5 microM atropine, 150 microM NG-monomethyl-arginine (L-NMMA), 50 microM NG-nitro-L-arginine methyl ester (L-NAME), 1 microM Fe2+, or 5 microM methylene blue. These inhibitory effects of L-NMMA, L-NAME, or atropine could be reversed partly by 50 microM L-arginine. The Fe2+ inhibition of H2O2-stimulated relaxation was reduced significantly by either 1 mM deferoxamine (a Fe2+ chelator) or 100 microM dimethyl sulfoxide (DMSO, a *OH scavenger). Such relaxant effects of H2O2 were enhanced, significantly, by an acetylcholinesterase antagonist, neostigmine. A variety of pharmacological antagonists (of diverse vasodilator agents) could not inhibit the relaxant action of H2O2. Our observations suggest that at suitable pathophysiological concentrations, H2O2 could induce release of an endothelium-derived relaxing factor (EDRF), probably nitric oxide (NO), from endothelial cells of the canine cerebral artery. The H2O2 relaxant effects are clearly Ca2+-dependent, require formation of cyclic guanosine monophosphate (cGMP), and may be associated with release of endogenous acetylcholine (ACh).
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PMID:Endothelium-dependent relaxation to hydrogen peroxide in canine basilar artery: a potential new cerebral dilator mechanism. 986 58

The effects of hydrogen peroxide (H2O2, 1 nM-5 mM) on the tone of the rings of aorta precontracted with phenylephrine (PE) were studied in 4-5 months streptozotocin (STZ)-diabetic rats and their age-matched controls. H2O2 induced brief contraction before relaxation in endothelium-containing rings that was more pronounced in diabetic rats. Removal of the endothelium or pretreatment of rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM) abolished H2O2-induced immediate and transient increase in tone, but preincubation with indomethacin (10 microM) had no effect on contractions induced by H2O2 in both group of animals. Pretreatment with L-NAME or indomethacin as well as absence of endothelium produced an inhibition of H2O2-induced relaxation that was more pronounced in diabetic rings. Chronically STZ-diabetes resulted in a significant increase in H2O2-induced maximum relaxation that was largely endothelium-dependent. Decreased sensitivity (pD2) of diabetic vessels to vasorelaxant action of H2O2 was normalized by superoxide dismutase (SOD, 80 U/ml). Pretreatment with SOD had no effect on H2O2-induced maximum relaxations in both group of animals but led to an increase in H2O2-induced contractions in control rats. When the rings pretreated with diethyldithiocarbamate (DETCA, 5 mM), H2O2 produced only contraction in control rats, and H2O2-induced relaxations were markedly depressed in diabetic rats. H2O2 did not affect the tone of intact or endothelium-denuded rings in the presence of catalase (2000 U/ml). Aminotriazole (AT, 10 mM) failed to affect H2O2-induced contractions or relaxations in all rings. Our observations suggest that increased production of oxygen-derived free radicals (OFRs) in diabetic state leads to a decrease in SOD activity resulting an increase in endogenous superoxide anions (O2*-), that is limited cytotoxic actions, and an increase in catalase activity resulting a decrease in both H2O2 concentrations and the production of harmful hydroxyl radical (*OH) in diabetic aorta in long-term. Present results indicate that increased vascular activity of H2O2 may be an important factor in the development of vascular disorders associated with chronically diabetes mellitus. Enhanced formation of *OH, that is a product of exogenous H2O2 and excess O2*, seems to be contribute to increased relaxations to exogenously added H2O2 in chronically diabetic vessels.
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PMID:Increased activity of H2O2 in aorta isolated from chronically streptozotocin-diabetic rats: effects of antioxidant enzymes and enzymes inhibitors. 1044 15

Although endothelium-derived hyperpolarizing factor (EDHF) is thought to be a cytochrome P-450 product (arachidonic acid metabolite) in some tissues, in porcine coronary arteries (PCAs) its nature remains unclear. Because phospholipase A2 and C are involved in the synthesis and/or release of EDHF in the PCA, the arachidonic acid (AA) pathway may be involved. In the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) and the NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME; 10(-4) M), both bradykinin (BK; 10(-9)-10(-6) M) and AA (10(-7)-10(-4) M) induced dose-dependent relaxation of PGF2alpha-contracted PCA rings, which was blocked by a high extracellular concentration of KCl (30 mM) or pretreatment with ouabain, a Na+/K+-adenosine triphosphatase (ATPase) inhibitor (5 x 10(-7) M). Eicosatetraynoic acid (ETYA; 20 microM), which inhibits all AA pathways, slightly affected the response to BK and AA; however, lipoxygenase or cytochrome P-450 inhibitors had no effect, suggesting that relaxation is independent of these enzymatic pathways. Because endothelial cells can generate reactive oxygen species (ROS) via metabolism of AA and independent of cyclooxygenase activity, we also studied (a) whether ROS can relax the PCA, as well as the mechanism(s) involved, and (b) the role of ROS in BK- and AA-induced relaxation. Xanthine (X; 100 microM) plus xanthine oxidase (XO; 0.02 U/ml) induced time-dependent relaxation of PGF2alpha-contracted PCA rings in the presence of indomethacin and L-NAME. Dilatation was not affected by superoxide dismutase (SOD; 500 U/ml) but was abolished by catalase (300 U/ml), suggesting that hydrogen peroxide (H2O2) is involved. When rings were contracted by depolarizing them with 30 mM KCl, X/XO failed to elicit relaxation. Ouabain abolished the response to X/XO, suggesting that X/XO may induce relaxation by hyperpolarizing vascular smooth muscle cells via stimulation of the Na+/K+-ATPase pump. We therefore questioned whether ROS might be involved in BK- and AA-induced relaxation. Because catalase combined with SOD had little or no effect, we concluded that in the PCA, the relaxation induced by BK via EDHF involves some mechanism independent of NO, AA metabolism, or ROS.
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PMID:Reactive oxygen species: role in the relaxation induced by bradykinin or arachidonic acid via EDHF in isolated porcine coronary arteries. 1051 Nov 33

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