Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is thought to play a critical role in the pathogenesis of hypertension. Protein oxidation is defined here as the covalent modification of a protein induced either directly by reactive oxygen species or indirectly by reaction with secondary by-products of oxidative stress. The aim of our study was to evaluate the protein oxidation and to examine the function of the antioxidative system in sustained and white coat hypertensives (WCH) and compare with normotensives. This study was designed to investigate the protein oxidation parameters [protein carbonyls (PCOs)] in sustained hypertensives (17 males and 20 females) and WCH (18 males and 19 females). PCO and the endogenous antioxidant components protein thiol (P-SH), CuZn-superoxide dismutase (CuZn-SOD) and glutathione (GSH) were analysed using spectrophotometric and kinetic methods. Sustained hypertensive and WCH groups exhibited higher protein oxidation and lower P-SH, CuZn-SOD and GSH activities than normotensives. With regard to these parameters, there was no significant difference between sustained hypertensive and WCH groups. Blood pressure correlates positively with PCO groups and negatively with others. There exists an imbalance between oxidants and antioxidants in WCH because of the increase of oxidants associated with the decrease of antioxidant capacity. This may cause endothelial dysfunction just like in sustained hypertension. It may be necessary to add antioxidants to conventional antihypertensive therapy to balance the oxidative status in WCH.
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PMID:Oxidative stress in human in sustained and white coat hypertension. 1710 61

When working on the regulation of prostacyclin synthase (PGIS), we found that PGIS was selectively inhibited by peroxynitrite (ONOO-), a potent oxidant formed by the combination of superoxide anion and nitric oxide (NO) at a rate of diffusion-controlled. None of the cellular antioxidants studied (i.e. GSH, Vitamins C and E, and others) prevented the inhibition of ONOO- on PGIS. This unexpected behavior was explained by a catalytic reaction of the iron-thiolate center of PGIS with ONOO- anion. In contrast, ONOO- activated both thromboxane A2-synthase and cyclooxygenases. In addition, we demonstrated that sub-micromolar levels of ONOO- inhibited PGI2-dependent vasorelaxation and triggered a PGH2-dependent vasospasm, indicating that ONOO- increased PGH2 formation as a consequence of PGIS nitration. We have subsequently demonstrated that endogenous ONOO- caused PGIS nitration and TxA2 activation in several diseased conditions such as atherosclerotic vessels, hypoxia-reperfusion injury, cytokines-treated cells, diabetes, as well as hypertension. Since NO is produced physiologically it seems that excessive formation of superoxide not only eliminates the vasodilatory, growth-inhibiting, anti-thrombotic and anti-adhesive effects of NO and PGI2 but also allows and promotes an action of the potent vasoconstrictor, prothrombotic agent, growth promoter, and leukocyte adherer, PGH2. We conclude that the nitration of PGIS nitration might be a new pathogenic mechanism for superoxide-induced endothelium dysfunction often observed in vascular diseases such as atherosclerosis, hypertension, ischemia, endotoxic shock, and diabetes.
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PMID:Peroxynitrite and protein tyrosine nitration of prostacyclin synthase. 1716 39

The aim of this study is to investigate GSTM1, GSTT1 and MTHFR genetic polymorphisms and its relation with total plasma glutathione (tGSH) levels in hypertension. Genotype distributions of GSTM1 and GSTT1 deletion polymorphisms and C677T variant of MTHFR were examined in a sample of 94 hypertensive patients with congestive heart failure and 207 healthy unrelated Portuguese individuals using PCR techniques. Plasma GST activity was determined spectrophotometrically. The antioxidant status was evaluated by fluorometric assays of tGSH. Genotype distributions of GSTT1 (chi2 test; p < 0.01) and MTHFR (chi2 test; p < 0.01) differ significantly between control and hypertensive patients with a greater prevalence of "non-null GSTT1/M1" and CT (heterozygous) genotypes. Moreover, GST activity and tGSH were markedly decreased in hypertension but there is no correlation with the studied polymorphisms. GSH depletion confirmed the possible involvement of oxidative stress in this pathology. Deletion of GSTT1 gene might be considered as protective factor for hypertension.
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PMID:GST M1/T1 and MTHFR polymorphisms as risk factors for hypertension. 1718 5

The present study was undertaken to evaluate the protective effect of thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, in rats after chronic inhibition of nitric oxide synthesis with N(omega)-nitro-l-arginine methyl esters (l-NAME). Rats were divided randomly into different treatment groups: control, l-NAME, TQ and l-NAME + TQ. Hypertension was induced by 4 weeks administration of l-NAME (50 mg/kg/day p.o.). TQ was administered alone or in combination with l-NAME and continued for 4 weeks. The animals were killed, and the serum and kidney tissues were isolated for the determination of creatinine and glutathione (GSH), respectively. Rats receiving l-NAME showed a progressive increase in systolic blood pressure compared with control rats. Concomitant treatment with TQ (0.5 and 1 mg/kg/day p.o.) reduced the increase in systolic blood pressure induced by l-NAME in a dose dependent manner. Kidney injury was demonstrated by a significant increase in serum creatinine and a decrease in GSH in kidney tissue from l-NAME treated rats. Treatment of rats with TQ decreased the elevated creatinine and increased GSH to normal levels. TQ inhibited the in vitro production of superoxide radical in enzymatic and non-enzymatic systems. In conclusion, TQ is effective in protecting rats against l-NAME-induced hypertension and renal damage possibly via antioxidant activity.
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PMID:Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive rats. 1723 76

Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Both bind to metallothionein and substitute for zinc, copper, and other trace metals reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common. Selenium antagonizes mercury toxicity. The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, CHD, MI, increased carotid IMT and obstruction, CVA, generalized atherosclerosis, and renal dysfunction with proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury, cadmium, and other heavy metals inactivate COMT, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to heavy metal toxicity. Cadmium concentrates in the kidney, particularly inducing proteinuria and renal dysfunction; it is associated with hypertension, but less so with CHD. Renal cadmium reduces CYP4A11 and PPARs, which may be related to hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc deficiency. Dietary calcium may mitigate some of the toxicity of cadmium. Heavy metal toxicity, especially mercury and cadmium, should be evaluated in any patient with hypertension, CHD, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, serum, etc. with baseline and provoked evaluation should be done.
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PMID:The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. 1740 90

1. Hypertension leads to oxidative stress, lipid and protein damage, apoptosis and impaired cardiac contractile function. However, impact of gender on these hypertension-associated abnormalities has not been elucidated. 2. The present study evaluated the oxidative stress, lipid/protein damage, apoptosis in heart and brain tissues as well as cardiomyocyte contractile function in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) of both genders. Oxidative stress, lipid peroxidation, protein damage and apoptosis were assessed by glutathione (GSH) : reduced glutathione (GSSG) ratio, malondialdehyde (MDA) levels, protein carbonyl levels and caspase-3 activity, respectively. Cardiomyocyte contractile function was examined including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening/relengthening (+/-dL/dt). The SHR cardiomyocytes displayed reduced PS and +/-dL/dt compared with gender-matched WKY counterparts. Male but not female SHR cardiomyocytes possessed longer resting cell length, normal TPS and prolonged TR90. All mechanical parameters were comparable between male and female WKY rats with the exception of a higher TR90 in females. Hypertension did not significantly affect the GSH : GSSG ratio in the heart and brain tissues of either gender. Brain from female WKY rats displayed a reduced GSH : GSSG ratio. The MDA levels were unchanged and elevated, respectively, in SHR heart and SHR brain tissues from both genders. Protein carbonyl formation and caspase-3 activity were elevated in male but not female SHR hearts. Nonetheless, brain protein carbonyl level and caspase-3 activity were unaffected by hypertension or gender. 3. In summary, these results suggest that gender affects hypertension-associated oxidative stress, lipid and protein damage, apoptosis in heart and brain tissues and cardiomyocyte contractile function.
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PMID:Influence of gender on oxidative stress, lipid peroxidation, protein damage and apoptosis in hearts and brains from spontaneously hypertensive rats. 1743 12

The aim of this study was to investigate the relationship between chronic ethanol-induced increase in blood pressure (BP) and alterations in the aortic nitric oxide (NO) and the antioxidant systems in rats. Male Fisher rats (200-250 g) were divided into two groups of six animals each and treated as follows: 1) control (5% sucrose, orally) daily for 12 weeks and 2) 20% ethanol (4 g/kg, orally) daily for 12 weeks. The BP (systolic, diastolic and mean) was recorded every week through tail-cuff method. The animals were sacrificed 12 weeks after treatments and thoracic aorta was collected and analysed. The results show that systolic, diastolic and mean BP was significantly elevated 12 weeks after ethanol ingestion in rats compared to control. The endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expressions were down-regulated (50-55% of control) leading to depletion of aortic NO levels (69% of control) in ethanol treated rats compared to control. The ratio of reduced to oxidized glutathione (GSH/GSSG) was significantly depleted (58% of control) in the aorta of ethanol-treated rats compared to control. The decrease in aortic GSH/GSSG ratio was good correlated with increase in BP (r = 0.69). The antioxidant enzymes: copper/zinc-superoxide dismutase (CuZn-SOD) and manganese (Mn)-SOD, catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly depressed (36-53% of control) in the aorta of ethanol-treated rats compared to control. The study concluded that chronic ethanol ingestion induces hypertension which relates to the vascular endothelial dysfunction on account of the down-regulation of aortic endothelial antioxidants and NO generating system in rats.
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PMID:Down regulation of aortic nitric oxide and antioxidant systems in chronic alcohol-induced hypertension in rats. 1762 67

Oxidative stress may initiate significant hepatocyte injury in subjects with fatty liver. We characterized changes in hepatic oxidative anti-oxidative parameters in rats given a fructose-enriched diet (FED) with and without medications to reduce blood pressure or plasma triglycerides. FED rats had an increase in malondialdehyde (MDA) concentration, a reduction in alpha-tocopherol concentration, a reduction in paraoxonase (PON) activity, an increase in glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) activity. Amlodipine increased PON and GSH-Px, but decreased GSSG-R activity and alpha-tocopherol concentration. Captopril decreased MDA concentration and the activity of both GSH-Px and GSSG-R, but increased alpha-tocopherol concentration and PON activity. Bezafibrate increased alpha-tocopherol concentration and PON activity, but decreased the activity of GSSG-R. Animals with fatty liver exhibit an increase in peroxidative stress but also a defect in anti-oxidative pathways. Drugs administered to treat hypertension and hypertriglyceridemia could lead to a variety of changes in the hepatic oxidative, anti-oxidative milieu.
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PMID:Effects of amlodipine, captopril, and bezafibrate on oxidative milieu in rats with fatty liver. 1771 May 47

The link between chronic alcohol consumption and cardiovascular injury including hypertension is well known. However, molecular mediators implicated with alcohol-induced elevation in blood pressure (BP) remain elusive. The aim of this study was to investigate the relationship of chronic ethanol-induced endothelial injury and elevation in BP with angiotensin II levels in rats. Male Fisher rats were divided into two groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) ethanol (4 g kg(-1), orally) daily for 12 weeks. The BP (systolic, diastolic, and mean) was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; blood and thoracic aorta were isolated and analyzed for aortic reactivity response, angiotensin II levels, and oxidative endothelial injury. The results show that the systolic, diastolic, and mean BP were significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to elevated angiotensin II levels in the plasma and aorta of alcohol treated group compared to control. The aortic NADPH oxidase activity, ratio of oxidized to reduced glutathione (GSSG/GSH) and lipid peroxidation significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), and vascular endothelial growth factor (VEGF) protein expressions were depressed in alcohol group compared to control. The phenylephrine-mediated vasoconstriction response was not altered, while acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol treated rats compared to control. It is concluded that chronic ethanol ingestion induces hypertension which is correlated with elevated tissue angiotensin II levels, activation of NADPH oxidase activity causing endothelial injury, depletion of endothelial NO generating system, and impaired vascular relaxation in rats.
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PMID:Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat. 1772 10

Hypothyroidism enhances the progression of atherogenesis. Furthermore, dyslipidemia, hypertension, and obesity are known risk factors for atherosclerosis. Oxidative stress is implicated in the pathogenesis of cardiovascular diseases. However, there are contradicting reports on the existence of oxidative stress in hypothyroidism. Thus, the aim of the study is to evaluate the presence of oxidative stress in hypothyroidism and, if so, its possible association with various coronary lipid risk factors. The present study was carried out in a group of 27 freshly diagnosed normotensive primary hypothyroid female patients in comparison with healthy subjects. Their body mass index (BMI), serum thyroid profile, lipid profile, glucose, protein carbonylation, thiobarbituric acid reactive substances (TBARS), and blood antioxidant enzyme levels were estimated. The TBARS and protein carbonylation were significantly higher in cases compared with those in controls. Reduced glutathione was lower and glutathione peroxidase was higher in the test group compared with those in controls. Various lipid risk factors for coronary artery disease were significantly higher among the hypothyroid women in comparison with those in controls. The level of TBARS correlated significantly with various lipid risk factors among the hypothyroid women even after correcting the effect of BMI. However, no significant associations were observed between BMI and these risk factors when the effect of TBARS was nullified. In hypothyroidism, the coronary lipid risk factors seem to be more associated with lipid peroxidation than BMI. In conclusion, the present study indicates the presence of oxidative stress in hypothyroid patients and its association with atherogenic dyslipidemia, which is independent of BMI.
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PMID:Association between oxidative stress and coronary lipid risk factors in hypothyroid women is independent of body mass index. 1788 44


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