Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.15.1.1 (superoxide dismutase)
 58,858 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelium-derived relaxing factor (EDRF) is a substance that is released by the vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine (AC). Superoxide anion (O2-) inactivates EDRF. It is well known that the endothelium-dependent vascular relaxations to AC are depressed in the aorta of spontaneously hypertensive rats (SHR). We studied the role of O2- on onset and maintenance of hypertension in SHR. Male 4- and 17-week old SHR (4SHR, 17SHR), and enalapril treated 17-week old SHR (5 mg/kg/day for 4 weeks: ETSHR), and age-matched normotensive Wistar-Kyoto rats (WKY; 4WKY, 17WKY) were used. Relaxation responses to AC or superoxide dismutase (SOD) were measured in isolated aortae from rats. Mean arterial pressure (MAP) was measured after injection of SOD in rats under conscious state. Systolic blood pressure of 4SHR, 17SHR, ETSHR, 4WKY, and 17WKY were 129 +/- 2 mmHg, 203 +/- 3 mmHg, 158 +/- 3 mmHg, 97 +/- 1 mmHg, and 138 +/- 2 mmHg, respectively. Although relaxation responses to AC were decreased in aortae from 4SHR, 17SHR, and ETSHR compared with those from age-matched WKY, relaxation responses to SOD dit not differ between SHR and corresponding WKY. Whereas the injection of SOD(10000 U/kg) elicited a significant reduction of MAP in 4SHR (-11 +/- 3 mmHg) and 17SHR (-24 +/- 5 mmHg), it has no effect in WKY. These data suggest that AC mediated endothelium-dependent relaxation is attenuated in SHR and that excessive O2- in the endothelium resulted from hypertension may contributes the decreased response in SHR.
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PMID:[Role of superoxide anion on onset and maintenance of hypertension in spontaneously hypertensive rats]. 133 77

The authors examined the activity of the antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GP) in the blood of patients with permanent essential hypertension and hypertensive crises and changes in the activity of these enzymes when monotherapy with the calcium antagonist corinfar was used. A total of 62 patients (age 52.7 +/- 0.7 years) with hypertension and 25 apparently healthy volunteers (age 43.9 +/- 0.7 years) were examined. The activity of SOD and GP was found to be decreased by 33 and 22%, respectively, in patients with permanent hypertension and by 40 and 32%, respectively, during hypertensive crises. When hypertension was treated with corinfar, the activity of COD and GP was increased by 10 and 18%, respectively. Concurrently, these patients had subjective and clinical improvement. The findings suggest that impaired lipid peroxidation makes a great contribution to the pathogenesis of essential hypertension. It can be assumed that the use of antihypertensive agents producing effects on the level of lipid peroxidation products and the enhancements of the activity of antioxidative enzymes.
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PMID:[Changes in the activity of antioxidant enzymes in patients with hypertension]. 140 12

Increases in urine concentration of specific proteins have been proposed as early indicators of deleterious changes in kidney function. Four urinary proteins (albumin, superoxide dismutase, transferrin and N-acetyl-beta-D-glucosaminidase) were measured in workers exposed to heavy metals and solvents. None of the workers had clinical evidence of renal disease or hypertension. Workers exposed to mercury had a significant increase in urinary transferring, superoxide dismutase levels were slightly increased in workers exposed to solvents and lead, follow-up of these workers is needed to confirm that these changes predict late clinical deterioration of kidney functions.
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PMID:Early detection of changes in kidney function in workers exposed to solvents and heavy metals. 142 16

The efficacy of pharmacologic agents for prevention and control of oxygen-derived free radical damage in ischemia-reperfusion injury of the spinal cord was assessed in a swine model of thoracic and thoracoabdominal aortic crossclamping. Animals were exposed to 30 minutes of ischemia that induced lethal, irreversible injury and paraplegia. The experimental groups were as follows: group A (n = 7), control group, receiving no pharmacologic intervention; group B (n = 7), deferoxamine 50 mg/kg/day administered intravenously over 3 to 4 hours before ischemia; group C (n = 7), allopurinol pretreatment 50 mg/kg/day for 3 days; and group D (n = 7), superoxide dismutase 60,000 units administered with 50,000 units before removal of the aortic crossclamp and 10,000 units over 10 minutes of reperfusion. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. The methods of assessment were neurologic by a modified Tarlov criteria and blood flow by radiolabeled microspheres. Results of blood flow assessment confirmed a true ischemic episode of 30 minutes for all animals in all groups. The blood flow fell significantly during ischemia (p less than 0.01) and a hyperemic response was evident in the early reperfusion period. All animals in control group A were paraplegic. The group B (deferoxamine) results were superior; 85% had grade III function on a modified Tarlov scale, with animals in the group standing and even walking with difficulty. Only one animal in this group had good movements of hind limbs but was unable to stand or walk. Neurologic recovery was limited in the allopurinol group (group C), with 85% showing slight neurologic recovery with limited movement of the hind limbs. The animals in the superoxide dismutase group (group D) all had good recovery, with strong motor response of hind limbs, but were not able to stand. In summary, the results of this experimental protocol confirmed the possible role of oxygen-derived free radicals in the pathophysiology of spinal cord injury, induced by aortic crossclamping. Moreover, it proved that ischemia-reperfusion injury could be altered by pharmacologic interventions.
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PMID:Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping. 149 87

To elucidate the role of oxygen free radicals and lipid peroxidation in the pathogenesis of early hypertension and atherosclerosis, we studied the native distribution of three primary arterial antioxidant enzymes (AEs). Specific immunohistochemical localization of superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) was examined in the arterial wall of New Zealand White rabbits: six sham-operated normotensive/normolipidemics (NT/NL), seven coarctation-induced hypertensive/normolipidemics (HT/NL), eight normotensive diet-induced hyperlipidemics (NT/HL), and six hypertensive/hyperlipidemics (HT/HL). All three AEs were confined primarily to the endothelium in NT/NL rabbit aortas. However, in HT and HL rabbits a greater proportion of the arterial wall, including the endothelium, inner media, and middle media, displayed immunolocalization of three AEs. Multiple linear-regression analysis revealed that more than 70% of the total variability in the depth of immunolocalization of arterial AEs could be explained by changes in blood pressure and/or total cholesterol. Also, levels of plasma and arterial cholesterol oxides were significantly different (p less than 0.05) in HT and HL rabbits compared with controls, with twofold increases in NT/HLs, threefold increases in HT/NLs, and fourfold increases in HT/HLs. We conclude that intense free-radical activity in the arterial wall of HT and HL animals is one possibility and that this occurs despite the presence of abundant AEs.
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PMID:Immunolocalization of native antioxidant scavenger enzymes in early hypertensive and atherosclerotic arteries. Role of oxygen free radicals. 155 32

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248-01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperbaric oxygen toxicity: role of thromboxane. 155 13

Acetylcholine evokes the simultaneous release of endothelium-derived relaxing and contracting factors in aortas from spontaneously hypertensive rats. Only relaxing factors are released in aortas from normotensive controls. Experiments were designed to determine whether inhibitors of endothelium-dependent relaxations modify endothelium-dependent contractions. Rings of thoracic aortas of normotensive and spontaneously hypertensive rats, with and without endothelium, were suspended in organ chambers for isometric tension recording. Oxyhemoglobin (a scavenger of endothelium-derived relaxing factor) and NG-monomethyl L-arginine (an inhibitor of nitric oxide formation) augmented the contractions to acetylcholine. Methylene blue (an inhibitor of soluble guanylate cyclase) and superoxide dismutase (a scavenger of superoxide anions) did not modify these contractions. The contractions in the presence of oxyhemoglobin or NG-monomethyl L-arginine, like those in untreated rings, were endothelium-dependent; they only occurred in aortas from spontaneously hypertensive rats and were abolished by indomethacin. The contractions to acetylcholine in the presence of oxyhemoglobin were not affected by superoxide dismutase or deferoxamine. These data suggest that endothelium-derived relaxing factor inhibits endothelium-dependent contractions to acetylcholine in the spontaneously hypertensive rat aorta, probably by chemical inactivation of the endothelium-derived contracting factor rather than by stimulation of guanylate cyclase or scavenging of oxygen-derived free radicals.
Hypertension 1992 May
PMID:Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta. 156 62

Although active oxygen species play important roles in the pathogenesis of various diseases, the molecular mechanism for oxygen toxicity in vascular diseases remains to be elucidated. Since endothelium-derived relaxing factor (EDRF) is inactivated by superoxide radicals in vitro, oxidative stress in and around vascular endothelial cells may affect the circulatory status of animals. To study the role of superoxide radicals and related enzymes, such as superoxide dismutase (SOD), in vascular diseases, we have developed a fusion protein (HB-SOD) consisting of human Cu/Zn-type SOD and a C-terminal basic peptide with high affinity for heparan sulfate on endothelial cells. When injected intravenously, HB-SOD bound to vascular endothelial cells, underwent transcellular transport, and localized within vascular walls by a heparin-inhibitable mechanism. The blood pressure of spontaneously hypertensive rats (SHR) but not normal animals was decreased significantly by HB-SOD. Heparin inhibited the depressor effect of HB-SOD. In contrast, native SOD had no effect on blood pressure of either SHR or normal rats. Neither H2O2-inactivated HB-SOD nor the C-terminal heparin-binding peptide showed such a depressor effect, suggesting that the catalytic function of HB-SOD is responsible for its depressor action. To know the source of superoxide radicals, we determined xanthine oxidase activity in the aorta and uric acid levels in the plasma. Although no appreciable difference in xanthine oxidase activity was found between the two animal groups, uric acid levels were significantly higher in SHR than in normal rats. Oxypurinol, a potent inhibitor of xanthine oxidase, also decreased the blood pressure of SHR but not of normal rats. These findings indicate that superoxide radicals in and around vascular endothelial cells play critical roles in the pathogenesis of hypertension of SHR.
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PMID:Does superoxide underlie the pathogenesis of hypertension? 165 94

Increased free radical activity has been implicated in the pathogenesis of pregnancy-induced hypertension. This article investigates whether changes in antioxidant systems contribute to this condition. Two extracellular (plasma thiols and ceruloplasmin) and two intracellular (red blood cell lysate thiols and red blood cell superoxide dismutase) antioxidant markers were assayed in 25 nonpregnant women, 16 pregnant women with normal blood pressure, 19 women with pregnancy-induced hypertension, and 13 women with proteinuric pregnancy-induced hypertension. In the normotensive pregnant group (in comparison with the nonpregnant group) the plasma thiol level was reduced (p less than 0.001) and the ceruloplasmin level raised (p less than 0.005), suggesting increased free radical activity. The lysate thiol level increased (p less than 0.005), which may reflect a compensatory protective response. In the hypertensive pregnant groups the lysate thiol rise was not present. These red blood cells may be more prone to oxidative stress. Whether this situation is a cause or an effect of oxidative stress in pregnancy-induced hypertension has yet to be elucidated.
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PMID:Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension. 175 Apr 63

The concentration of human serum superoxide dismutase-1 (hSOD-1) containing copper and zinc ions were measured by radioimmunoassay healthy nonpregnant women, 15 normal pregnant women, 15 patients with mild to moderate hypertension (MMHSP) and 15 with severe hypertensive syndrome of pregnancy (SHSP). The mean serum hSOD-1 concentration in nonpregnant women was 148.84 +/- 60.53 (x +/- s) micrograms/L; while in the other 3 groups it was 394.19 +/- 122.21 micrograms/L, 377.12 +/- 173.45 micrograms/L and 581.15 +/- 118.50 micrograms/L. The results suggest that harmful free radicals increase gradually and a strong body defence system against oxidation damage of tissue cells is produced in the course of normal pregnancy and MMHSP. With cardionatrin treatment serum hSOD-1 concentrations of patients ameliorated returned to the level of normal pregnancy. The results indicate that there is a positive correlation between cardionatrin and hSOD-1 levels (r = 0.569, P less than 0.05), and a physiological regulation of the defence system exists, which may be related to the white blood cells. Hence, hSOD-1 probably plays a significant role in defence during normal pregnancy and hypertensive syndrome of pregnancy (HSP).
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PMID:Significance of changes in serum superoxide dismutase level in hypertensive syndrome of pregnancy. 183 17


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