Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension, cigarette smoking, and nicotine augment the clinical significance of other risk factors associated with cardiovascular diseases by mechanisms which are poorly understood. Since altered trace element metabolism and antioxidant status have also been implicated in these diseases, the present study investigated the interaction of nicotine treatment and hypertension on tissue trace element concentrations and select indices of antioxidant status. Spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with nicotine, via a time release tablet at an average rate of 75 micrograms/h for 6 weeks. Systolic blood pressure in nicotine-treated SHRs was significantly higher at weeks 3 and 6 of treatment than in the SHR-controls. Blood pressure in WKY rats was not affected by nicotine. Plasma and liver iron concentrations in the nicotine-treated SHR were higher than the SHR-controls and the WKY groups. Nicotine treatment did not affect plasma and liver zinc and copper concentrations or liver manganese (Mn) concentrations. Plasma ceruloplasmin activity was increased by nicotine treatment in the SHRs. Liver Mn superoxide dismutase (MnSOD) activities and glutathione concentrations, and liver and heart glutathione reductase activities, were higher in both groups of SHRs than in the WKY groups. Red cell SOD activity in the nicotine-treated SHR was lower than in the SHR-controls. In summary, blood pressure increased more rapidly in the nicotine-treated SHRs compared to the controls. The marked effects on antioxidant status observed were attributable more to hypertension than to the nicotine treatment.
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PMID:Comparative effects of 6-week nicotine treatment on blood pressure and components of the antioxidant system in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. 774 May 54

The activities of glomerular intrinsic antioxidant enzymes (AOEs) were measured in a diabetic spontaneously hypertensive rat (SHR) model. The effects of antihypertensive drugs, i.e. captopril or triple therapy (hydralazine, reserpine, and hydrochlorothiazide), on glomerular intrinsic AOE activities in this model were evaluated. The effects of blood glucose control on the AOE activities were also determined. The aim of the present study was to determine whether activities of glomerular intrinsic AOEs might correlate with disease activity in diabetic SHR. This study showed a decrease of glomerular intrinsic AOE, i.e. Cu/Zn-SOD and Mn-SOD (SOD = superoxide dismutase), glutathione peroxidase, and catalase, activities in diabetic SHR. Glomerular Cu/Zn-SOD or Mn-SOD, glutathione peroxidase, and catalase activities in nondiabetic SHR were slightly lower than those in nondiabetic WKY rats. These activities in diabetic SHR were significantly improved after captopril or triple therapy or blood glucose control. The levels of urinary albumin excretion, creatinine clearance, and glomerular tuft areas in diabetic SHR were also improved after the therapy. It appears that hypertension and hyperglycemia may influence the glomerular intrinsic AOE activities, albuminuria, creatinine clearance, and glomerular tuft areas in diabetic SHR. Thus, it is indicated that control of blood pressure or blood glucose is a very important factor for preventing renal injuries in the diabetic SHR model.
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PMID:Effects of antihypertensive drugs or glycemic control on antioxidant enzyme activities in spontaneously hypertensive rats with diabetes. 922 34

Insulin resistance and hyperinsulinemia have recently been identified as independent determinants of several risk factors for cardiovascular disease. The generation of reactive oxygen species (ROS) may play an important role as a final common mediator by which glucose and insulin resistance might contribute to development of cardiovascular disease and hypertension. The aim of the present study was to evaluate changes on mRNA expression of antioxidant enzymes [catalase, Cu-Zn superoxide dismutase (Cu-ZnSOD), MnSOD], blood pressure and metabolic parameters in insulin resistance that follow feeding normotensive Wistar rats a high-fructose-enriched diet. In our investigation 26 normal male Wistar rats were fed a high-fructose diet for 2 weeks (no.=14) or normal chow to serve as a control group (no.=12). In vivo insulin resistance was verified in a subgroup of control and fructose-fed rats by the euglycemic hyperinsulinemic clamp technique at 2 different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol/kg/min respectively. The glucose infusion rate (GIR) was not significantly different in the two groups during the submaximal infusion of insulin (1.4 +/- 0.8 mmol/kg/min in fructose-fed rats vs 1.6 +/- 0.7 mmol/kg/min in control rats, NS) while in fructose-fed rats it was significantly lower (-29.8%) than in control rats during maximal infusion of insulin (2.6 +/- 0.3 mmol/kg/min vs 3.7 +/- 0.3 mmol/kg/min, p<0.05). Fructose feeding markedly reduced the expression of catalase mRNA and Cu-ZnSOD mRNA in the liver, catalase mRNA in the heart (p<0.05). A tendency of fructose feeding to reduce the expression of antioxidant enzymes in skeletal muscle and adipose tissue was also observed (NS). Fructose feeding also increased plasma uric acid (119.9 +/- 30.4 vs 42.1 +/- 10 pmol/l, p<0.05) and systemic blood pressure (128 +/- 4 vs 109 +/- 5 mmHg, p<0.05) respect to control animals. No significant changes were observed in plasma levels of glycemia and tryglycerides. Our study suggests that in non-hyperglycemic, fructose-fed insulin-resistant rats the expression of catalase is inhibited in liver and heart. This condition might lead to higher susceptibility to oxidative stress in insulin resistance. However, an adaptive cellular response to maintain the effectiveness of intracellular signaling pathways mediated by insulin-activated hydrogen peroxide generating systems may also be hypothesized.
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PMID:High-fructose diet decreases catalase mRNA levels in rat tissues. 1181 7

Gene transfer may be appropriate for therapeutic protocols targeted at the vascular endothelium. Endothelial dysfunction is the principal phenotype associated with atherosclerosis and hypertension. Oxidative stress has been implicated in the development of endothelial dysfunction. We have explored the ability of overexpressing anti-oxidant genes (superoxide dismutases; SODs) in vitro and in vivo to assess their potential for reversing endothelial dysfunction in a rat model, the stroke-prone spontaneously hypertensive rat (SHRSP). Western blotting and immunofluorescence assays in vitro showed efficient overexpression of MnSOD and ECSOD with respect to localisation to the mitochondria and extracellular surface, respectively. Transgene functional activity was quantified with SOD activity assays. MnSOD and ECSOD overexpression in intact SHRSP vessels in vivo led to endothelial and adventitial overexpression. Pharmacological assessment of transduced vessels following in vivo delivery by basal NO availability quantification demonstrated that the "null" adenovirus and MnSOD adenovirus did not significantly increase NO availability. However, AdECSOD-treated carotid arteries showed a significant increase in NO availability (1.91 +/- 0.04 versus 0.75 +/- 0.08 g/g, n = 6, P = 0.029). In summary, efficient overexpression of ECSOD, but not MnSOD in vivo, results in improved endothelial function in a rat model of hypertension and has important implications for the development of endothelial-based vascular gene therapy.
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PMID:Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension. 1185 69

Hypertension is an age-dependent disorder. Oxidative stress has been suggested to play a role in aging and age-dependent disorders. The objective of this study is to examine the oxidant and antioxidant status in the aorta of a mouse model with high blood pressure (BPH). Our results showed that the level of malondialdehyde (MDA) in the aorta of BPH mice was approximately 2.6-fold higher than that of the normal blood pressure (BPN) mice, suggesting an increased in vivo oxidative stress in the arterial wall of BPH mice. In addition, the release of hydrogen peroxide (H2O2) from the aorta of BPH mice was significantly faster than that of BPN mice. To determine if the increased H2O2 release is related to a down-regulation of antioxidant enzymes in the arterial wall, we measured the activities of the major antioxidant enzymes in mouse aortas. We observed that the activities of Cu/Zn-superoxide dismutase (SOD) and glutathione peroxidase-1 in BPH mice were similar to BPN mice. On the other hand, the catalase activity in the aorta of BPH mice was significantly reduced while the activities of Mn-SOD and extracellular (EC)-SOD in the aorta of BPH mice were significantly elevated as compared with BPN mice. These results suggest that increase in SOD activity and decrease in catalase activity might be responsible for the increased release of H2O2 in the arterial wall of BPH mice.
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PMID:Elevation of oxidative stress in the aorta of genetically hypertensive mice. 1287 44

We have demonstrated recently [Callera, Touyz, Teixeira, Muscara, Carvalho, Fortes, Schiffrin and Tostes (2003) Hypertension 42, 811-817] that increased vascular oxidative stress in DOCA (deoxycorticosterone acetate)-salt rats is associated with activation of the ET (endothelin) system via ETA receptors. The exact source of ET-1-mediated oxidative stress remains unclear. The aim of the present study was to investigate whether ET-1 increases generation of ROS (reactive oxygen species) in DOCA-salt hypertension through NADPH-oxidase-dependent mechanisms. Xanthine oxidase, eNOS (endothelial nitric oxide synthase) and COX-2 (cyclo-oxygenase-2) were also examined as potential ET-1 sources of ROS as well as mitochondrial respiration. DOCA-salt and control UniNX (uninephrectomized) rats were treated with the ETA antagonist BMS182874 (40 mg.day(-1).kg(-1) of body weight) or vehicle. Plasma TBARS (thiobarbituric acid-reacting substances) were increased in DOCA-salt compared with UniNX rats. Activity of NADPH and xanthine oxidases in aorta, mesenteric arteries and heart was increased in DOCA-salt rats. BMS182874 decreased plasma TBARS levels without influencing NADPH and xanthine oxidase activities in DOCA-salt rats. Increased p22(phox) protein expression and increased p47(phox) membrane translocation in arteries from DOCA-salt by rats were not affected by BMS182874 treatment. Increased eNOS and COX-2 expression, also observed in aortas from DOCA-salt rats, was unaltered by BMS182874. Increased mitochondrial generation of ROS in DOCA-salt rats was normalized by BMS182874. ETA antagonism also increased the expression of mitochondrial MnSOD (manganese superoxide dismutase) in DOCA-salt rats. In conclusion, activation of NADPH oxidase does not seem to be the major source of oxidative stress induced by ET-1/ETA in DOCA-salt hypertension, which also appears to be independent of increased activation of xanthine oxidase or eNOS/COX-2 overexpression. Mitochondria may play a role in ET-1-driven oxidative stress, as evidenced by increased mitochondrial-derived ROS in this model of hypertension.
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PMID:Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms. 1632 76

The study aim was to investigate the interaction of physical conditioning and chronic ethanol ingestion on blood pressure (BP), heart rate (HR), nitric oxide (NO) and oxidants/antioxidants balance in the plasma of rats. Male Fisher rats were divided into four groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks; (2) ethanol (4 g kg(-1), orally) daily for 12 weeks; (3) exercise training on treadmill plus sucrose daily for 12 weeks and (4) exercise training on treadmill followed by ethanol (4 g kg(-1), orally) daily for 12 weeks. The body weight, BP and HR were recorded every week. The animals were sacrificed under ether anesthesia after 12 weeks, blood collected in heparinzed vials, plasma isolated and analyzed. The results show that exercise training significantly lowered the weight gain 6-12 weeks in ethanol treated rats compared to ethanol alone or control rats. The mean arterial BP was significantly elevated 6-12 weeks after ethanol ingestion without significant alterations in HR. Exercise training lowered the BP close to the normal control values in ethanol fed rats. Ethanol significantly decreased the plasma NO levels, reduced to oxidized glutathione ratio (GSH/GSSG) and antioxidant enzymes-superoxide dismutase (CuZn-SOD, and Mn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities while plasma NADPH oxidase activity and malondialdehyde (MDA) levels were significantly elevated compared to control. Exercise training significantly restored the depletion of plasma NO levels, GSH/GSSG ratio, and antioxidant enzyme activities and normalized the MDA levels and NADPH oxidase activity in the plasma of ethanol treated rats. The study concluded that physical conditioning attenuates the chronic ethanol-induced hypertension by augmenting the NO bioavailability and reducing the oxidative stress response in the plasma of rats.
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PMID:Physiological basis for effect of physical conditioning on chronic ethanol-induced hypertension in a rat model. 1671 71

We previously found that angiotensin II-induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD(-/-) and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD(-/-) compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD(-/-) than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD(-/-) mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD(-/-) mice, the activity of Cu/ZnSOD was increased by 80% after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II-induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD(-/-) mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in hypertension.
Hypertension 2006 Sep
PMID:Role of extracellular superoxide dismutase in hypertension. 1689 57

The renal and cardiac benefits of renin-angiotensin system (RAS) inhibition in hypertension exceed those attributable to blood pressure reduction, and seem to involve mitochondrial function changes. To investigate whether mitochondrial changes associated with RAS inhibition are related to changes in nitric oxide (NO) metabolism, four groups of male Wistar rats were treated during 2 wk with a RAS inhibitor, enalapril (10 mg x kg(-1) x day(-1); Enal), or a NO synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) (1 mg x kg(-1) x day(-1)), or both (Enal+L-NAME), or were untreated (control). Blood pressure and body weight were lower in Enal than in control. Electron transfer through complexes I to III and cytochrome oxidase activity were significantly lower, and uncoupling protein-2 content was significantly higher in kidney mitochondria isolated from Enal than in those from control. All of these changes were prevented by L-NAME cotreatment and were accompanied by a higher production/bioavailability of kidney NO. L-NAME abolished mitochondrial NOS activity but failed to inhibit extra-mitochondrial kidney NOS, underscoring the relevance of mitochondrial NO in those effects of enalapril that were suppressed by L-NAME cotreatment. In Enal, kidney mitochondria H(2)O(2) production rate and MnSOD activity were significantly lower than in control, and these effects were not prevented by L-NAME cotreatment. These findings may clarify the role of NO in the interactions between RAS and mitochondrial metabolism and can help to unravel the mechanisms involved in renal protection by RAS inhibitors.
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PMID:Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney. 1718 9

Interactions of free radicals such as superoxide (O2-), nitric oxide (NO), and peroxynitrite (ONOO-) are important in pathophysiological conditions such as hypertension, atherosclerosis, diabetes and the resulting cardiovascular diseases. Excessive levels of superoxide during oxidative stress cause a reduction in NO bioavailability by forming peroxynitrite and resulting in endothelial dysfunction. Superoxide dismutase (SOD) competes with NO for superoxide, and reduces the formation of peroxynitrite. In this study, we developed a mathematical model for free radical transport within and around an arteriolar vessel based on the fundamental principles of mass balance, reaction kinetics, and vascular geometry. We used the model to study the effect of the three types of SOD, viz. CuZn-SOD, Mn-SOD and extra cellular-SOD, on the bioavailability of NO. Results indicate that SOD location and concentration in the arteriole significantly affect superoxide concentration. The model predicts that a reduction in SOD levels results in increased superoxide and peroxynitrite concentrations and decreased NO concentration in the vessel. The results also suggest a role of SOD in the amelioration of oxidative stress and NO bioavailability in microcirculation. This model will help in furthering our knowledge of endothelial dysfunction in pathological conditions and the impact of specific SODs on free radical interactions.
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PMID:Impact of superoxide dismutase on nitric oxide and peroxynitrite levels in the microcirculation--a computational model. 1800 34


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