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)

To study the mechanism of the fall of glutathione peroxidase (GSH-Px) activity in erythrocyte after cerebral strokes in stroke-prone spontaneously hypertensive rats (SHRSP), erythrocytes were fractionated into low density erythrocytes (LD-E) and high density erythrocytes (HD-E) by a density gradient centrifugal method using Percoll solution, and fluctuation of the distribution ratio and changes of GSH-Px activity in fractionated erythrocytes were investigated. The distribution ratio of LD-E and HD-E in erythrocytes of SHRSP was about 4:1 at 5 weeks of age (n = 6), and the distribution to HD-E increased along with aging. While the distribution ratio was changed, however, there was no change in the GSH-Px activity in both LD-E and HD-E of erythrocytes. In senile, 30-week-old SHRSP (n = 4) with advanced hypertension, the GSH-Px activity in the HD-E was lower, in proportion to the increase of the distribution rate against HD-E. On the other hand, in SHRSP (n = 5) having cerebral stroke, the distribution ratio of LD-E and HD-E was about 1:4. The GSH-Px activity was 31.4 +/- 2.9 units/10(10) erythrocytes in LD-E, which was hardly different from the value of SHRSP without stroke (35.7 +/- 3.3 units/10(10) erythrocytes). In HD-E, however, the activity was 18.2 +/- 2.2 units/10(10) erythrocytes, being lower than the activity of SHRSP without stroke. At the moment when the GSH-Px activity had dropped to 17 units/mg hemoglobin, and the control diet was changed to one based on fish or a hydralazine treatment given, the activity recovered, and an increase in body weight and the distribution rate of the LD-E over HD-E was increased. It is clear from these experiments that the fall of erythrocyte GSH-Px activity observed after cerebral stroke is due to a decrease of LD-E and increase of HD-E, which has lowered activity. However, nothing definite is known on the relationship between the fall of GSH-Px activity in erythrocytes and disorder in cerebral tissue. It appears that the fall of the GSH-Px activity causes at least functional and structural changes in erythrocytes, which interfere with the delivery of oxygen to peripheral tissues, triggering oxidation stress in cerebral tissues.
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PMID:Cell age distribution of erythrocytes at the incidence of cerebral stroke in stroke-prone spontaneously hypertensive rats, and their glutathione peroxidase activity. 957 77

Plasma and lipoprotein lipid composition and endogenous hepatic antioxidant status were investigated in hypertensive, 14-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Total plasma calcium and magnesium concentrations were similar between both rat strains; however, systolic blood pressure in SHR was greater than in WKY at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg; p < or = 0.05), confirming hypertension in SHR. Total plasma cholesterol and triacylglycerol concentrations were lower (p < or = 0.05) in SHR compared with WKY. A lower (p < 0.05) HDL cholesterol level in SHR plasma resulted in a higher LDL to HDL cholesterol ratio compared with WKY counterparts. No significant differences in the relative proportion of HDL apolipoprotein A-I fraction were observed between SHR and WKY. Both SHR VLDL and HDL triacylglycerol fractions were lower (p < 0.05) in SHR than WKY. Analysis of liver antioxidant enzyme activities showed no differences in rat liver superoxide dismutase (SOD), but lower (p < 0.05) liver glutathione peroxidase (GSH-Px) activity in SHR. However, liver glutathione (GSH) levels were similar in SHR and WKY counterparts. A possible compensatory effect to the oxidative status of SHR was suggested by the significant (p < 0.05) increase in both liver catalase (CAT) and glutathione reductase (GSSG-Red) activities. Despite these results, in vitro oxidative challenge studies with H2O2 demonstrated a greater susceptibility of liver to GSH depletion in the SHR, although no parallel change in thiobarbituric acid reactive substances (TBARS) production was observed. The comparatively lower plasma cholesterol observed in hypertensive SHR paralleled specific differences in liver catalase and glutathione redox antioxidant enzyme activities.
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PMID:Plasma and lipoprotein lipid composition and hepatic antioxidant status in spontaneously hypertensive (SHR) and normotensive (WKY) rats. 963 61

This study is aimed at examining whether essential arterial hypertension (HTN) or ACE inhibitors have any effect on erythrocyte selenium (Se)-dependent and Se-non-dependent glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity. Eleven patients with HTN (2 men and 9 women) and 9 healthy volunteers were included in this study after clinical examination and laboratory investigation. The activities of all three enzymes were determined and then the patients were assigned to receive ACE inhibitor therapy consisting of captopril, 25 to 50 mg daily, or enalapril, 10 to 40 mg daily. After 1 year, the determination of antioxidant enzymes was repeated. Our results showed that the initial values of Se-dependent GSH-Px in patients treated with ACE inhibitors were significantly lower (19.60 +/- 3.50 microM NADPH/min(-1)/mgHb(-1)) compared with the controls (28.64 +/- 4.93 microM NADPH/min(-1)/mgHb(-1); p < 0.001), whereas the activity of Se-non-dependent GSH-Px was significantly enhanced (13.55 +/- 1.46 microM NADPH/min(-1)/mgHb(-1); p < 0.001) compared with the control group (9.44 +/- 0.81 microM NADPH/min(-1)/mgHb(-1); p < 0.001). ACE inhibitors did not significantly change the activity of Se-dependent GSH-Px or Se-non-dependent GSH-Px. No significant alteration was observed in SOD activity.
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PMID:Selenium-dependent GSH-Px in erythrocytes of patients with hypertension treated with ACE inhibitors. 972 2

The purpose of this study was to examine the relationship between arterial hypertension (HTN), chronic heart disease (CHD), and selenium (Se) status. Blood and plasma Se concentrations and Se-dependent GSH-Px activities were determined in 40 patients (HTN = 20; CHD = 20) and 17 healthy volunteers aged 41 to 66 years. Whole blood and plasma Se concentrations were significantly lower in the patients with HTN (19.1% and 26.3%, respectively) and CHD (33.1% and 29.4%, respectively) compared with the values obtained in the controls. The hypertensive patients had lower plasma Se-GSH-Px (26.7%), and those with CHD had both lower whole blood (19.5%) and plasma Se-GSH-Px activities (30.2%). A significant positive correlation between plasma Se-GSH-Px activity and ejection fraction (EF) was found in patients with CHD. There were significant correlations between plasma and whole blood Se concentration, plasma Se concentration and Se-GSH-Px activity, and whole blood Se and Se-GSH-Px activity. Our results showed that hypertensive patients and those with CHD had lower Se levels compared with controls. We conclude that low Se content might be a risk factor for development of HTN and CHD.
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PMID:Blood and plasma selenium levels and GSH-Px activities in patients with arterial hypertension and chronic heart disease. 972 4

The effects of varying dietary fat saturation [butter (B), beef tallow (BT)] or polyunsaturation [(n-6) soybean oil (SBO), (n-3) menhaden oil (MO)] and cholesterol content (0.05 and 0.5 g/100 g) on systolic blood pressure (SBP), plasma lipids and tissue antioxidant status were investigated in 14-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Varying dietary fat composition for 9 wk had no influence on SBP in either SHR or WKY rats. Rats fed MO diets exhibited smaller (P < 0.05) body weight gains, lower (P < 0.05) feed efficiency ratios and lower (P < 0.05) plasma cholesterol concentrations than those fed the B, BT and SBO diets. Significant (P < 0.05) interactions for animal strain x cholesterol intake and animal strain x fat source were noted for serum cholesterol concentrations. SHR exhibited higher (P < 0.05) RBC and liver catalase (CAT), and heart and liver superoxide dismutase (SOD) activities similar to those of WKY rats. The lower (P <0.01) RBC, heart and liver glutathione peroxidase (GSH-Px) activities observed in SHR coincided with higher (P <0.01) glutathione reductase (GSSG-Red), compared with WKY rats. Dietary cholesterol intake had no effect on RBC, heart and liver total sulfhydryl concentration or GSH-Px activities, but increased (P <0. 001) liver GSSG-Red. Feeding MO resulted in lower (P <0.001) RBC and heart GSH-Px activities. In contrast, feeding B and BT resulted in lower GSH-Px in liver. The significant (P < 0.01) animal strain x fat source interaction obtained for liver GSH-Px activity indicated that SHR responded differently to polyunsaturated fatty acid feeding than their WKY counterparts. Diet-induced changes in tissue antioxidant status were tissue specific and did not affect the development of hypertension in SHR.
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PMID:Variations in dietary fat and cholesterol intakes modify antioxidant status of SHR and WKY rats. 977 27

High resolution B-mode ultrasonography of the carotid arteries has been used to investigate the signs of early atherosclerotic vessel wall disease by measuring the intima-media thickness (IMT). We examined the association between IMT and lipid peroxidation and found IMT to be increased in a group of patients with respect to controls (1.430+/-0.341 mm versus 0.703+/-0.201 mm, P < 0.001). Plasma and erythrocyte malondialdehyde (MDA) levels were also significantly higher (P<0.001) and the erythrocyte reduced glutathione (GSH) levels were significantly lower (P <0.001) in the patients with respect to the controls. In the groups of patients there was no significant correlation between the mean IMT and the plasma and erythrocyte MDA levels or the erythrocyte GSH levels. In conclusion determination of lipid peroxides would be especially important and advisable in patients with increased carotid IMT. Type II diabetes and hypertension were also associated with increased IMT.
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PMID:A study on the carotid artery intima-media thickness and its association with lipid peroxidation. 977 48

It has been reported that the production of oxygen radicals mediated by xanthine oxidase (XO) is stimulated in hypertensive cardiovascular endothelium, suggesting involvement of oxidative stress in pathogenesis of hypertension. In this study we estimated the effect of nicardipine, a calcium blocker, on the oxidative stress and antioxidant activities in left ventricles from spontaneously hypertensive rat (SHR) and stroke-prone SHR (SHRSP). The activity of XO increased 3.5-fold in SHR and 6.2-fold in SHRSP compared to that in normal controls (WKY). Interestingly, the levels of glutathione (GSH) and the activity of its synthesizing enzyme (gamma-glutamylcysteine synthetase, gamma-GCS) elevated concomitantly in SHR and SHRSP: the level of GSH increased 1.2-fold in SHR and 1.3-fold in SHRSP. The activity of gamma-GCS was elevated 1.5-fold in SHR and 2.4-fold in SHRSP, accompanying an increase in the expression of its mRNA. Treatment of these rats with nicardipine, for 4 weeks improved blood pressure, from 176 +/- 10 to 140 +/- 8 mmHg in SHR, and from 201 +/- 11 to 167 +/- 5 mmHg in SHRSP, respectively, and decreased wet weight of heart, levels of GSH, and the activities of XO and gamma-GCS. Nicardipine reduced the expression of gamma-GCS mRNA. Collectively, these results suggest that reactive oxygen species produced by XO in hypertensive rat heart cause induction of the expression of gamma-GCS and nicardipine plays a role in reducing the oxidative stress in hypertensive heart.
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PMID:Nicardipine normalizes elevated levels of antioxidant activity in response to xanthine oxidase-induced oxidative stress in hypertensive rat heart. 979 May 16

Recent evidence suggests that the endogenous antioxidant glutathione may play a protective role in cardiovascular disease. To directly investigate the role of glutathione in the regulation of glucose metabolism in hypertension, we studied the acute effects of in vivo infusions of this antioxidant (alone or in combination with insulin) on whole body glucose disposal (WBGD) using euglycemic glucose clamp and the effects on total red blood cell intracellular magnesium (RBC-Mg) in hypertensive (n=20) and normotensive (n=30) subjects. The relationships among WBGD, circulating reduced/oxidized glutathione (GSH/GSSG) levels, and RBC-Mg in both groups were evaluated. The in vitro effects of glutathione (100 micromol/L) on RBC free cytosolic magnesium (Mg(i)) were also studied. In vivo infusions of glutathione (15 mg/minx120 minutes) increased RBC-Mg in both normotensives and hypertensives (1.99+/-0.02 to 2.13+/-0.03 mmol/L, P<0.01, and 1.69+/-0.03 to 1.81+/-0.03 mmol/L, P<0.01, respectively). In vitro GSH but not GSSG increased Mg(i) (179+/-3 to 214+/-5 micromol/L, P<0.01). In basal conditions, RBC-Mg values were related to GSH/GSSG ratios (r=0.84, P<0.0001), and WBGD was directly, significantly, and independently related to both GSH/GSSG ratios (r=0.79, P<0.0001) and RBC-Mg (r=0.89, P<0.0001). This was also true when hypertensive and control groups were analyzed separately. On multivariate analysis, basal RBC-Mg (t=6.81, P<0.001), GSH/GSSG (t=3. 67, P<0.02), and blood pressure (t=2.89, P<0.05) were each independent determinants of WBGD, with RBC-Mg explaining 31% of the variability of WBGD. These data demonstrate a direct action of glutathione both in vivo and in vitro to enhance intracellular magnesium and a clinical linkage between cellular magnesium, GSH/GSSG ratios, and tissue glucose metabolism.
Hypertension 1999 Jul
PMID:Effects of glutathione on red blood cell intracellular magnesium: relation to glucose metabolism. 1040 27

Vitamin E is an antioxidant that has been demonstrated to improve insulin action. Glutathione, another natural antioxidant, may also be important in blood pressure and glucose homeostasis, consistent with the involvement of free radicals in both essential hypertension and diabetes mellitus. Our group has recently suggested that the effects of reduced glutathione on glucose metabolism may be mediated, at least in part, by intracellular magnesium levels (Mg([i])). Recent evidence suggests that vitamin E enhances glutathione levels and may play a protective role in magnesium deficiency-induced cardiac lesions. To directly investigate the effects of vitamin E supplementation on insulin sensitivity in hypertension, in relation to the effects on circulating levels of reduced (GSH) and oxidized (GSSG) glutathione and on Mg([i]), we performed a 4-week, double-blind, randomized study of vitamin E administration (600 mg/d) versus placebo in 24 hypertensive patients and measured whole-body glucose disposal (WBGD) by euglycemic glucose clamp, GSH/GSSG ratios, and Mg([i]) before and after intervention. The relationships among WBGD, GSH/GSSG, and Mg([i]) in both groups were evaluated. In hypertensive subjects, vitamin E administration significantly increased WBGD (25.56+/-0.61 to 31.75+/-0.53 micromol/kg of fat-free mass per minute; P<0.01), GSH/GSSG ratio (1.10+/-0.07 to 1.65+/-0.11; P<0.01), and Mg([i]) (1.71+/-0.042 to 1.99+/-0.049 mmol/L; P<0.01). In basal conditions, WBGD was significantly related to both GSH/GSSG ratios (r=0.58, P=0.047) and Mg([i]) (r=0.78, P=0.003). These data show a clinical link between vitamin E administration, cellular magnesium, GSH/GSSG ratio, and tissue glucose metabolism. Further studies are needed to explore the cellular mechanism(s) of this association.
Hypertension 1999 Oct
PMID:Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. 1052 98

Glucocorticoid-remediable aldosteronism (GRA) is a rarely recognised cause of arterial hypertension. We report the features of a 13-year-old boy with hypertension (casual blood pressure (BP) 140-180/95-110 mm Hg) discovered during a routine paediatric check. Ambulatory BP monitoring (ABPM) revealed significant hypertension with an abolished nocturnal BP fall (mean daytime BP 155/108 mm Hg, mean night-time BP 156/104 mm Hg, nocturnal BP fall 0/4%) which was indicative of secondary hypertension. Despite triple antihypertensive drug therapy the hypertensive control was unsatisfactory. Laboratory tests revealed hypokalaemia (3.0 mmol/l), suppressed plasma renin activity (0.012 nmol/l/h) and high plasma aldosterone (1.190 nmol/l). The diagnosis of primary hyperaldosteronism was established and GRA was further confirmed by the presence of the chimaeric GRA-gene and dexamethasone therapy was initiated. During the next 2 months of dexamethasone therapy all three antihypertensive drugs were discontinued and BP remained under control with restoration to a normal nocturnal BP fall (mean daytime BP 129/77 mm Hg, mean night-time BP 113/64, nocturnal BP fall 12/17%). A change of therapy from dexamethasone to spironolactone was necessary due to the side effects of corticosteroids after 3 months. Spironolactone alone (0.8-2 mg/kg/day) was able to control the BP sufficiently. In conclusion, to our knowledge, this is the first reported case of abolished nocturnal BP fall in a patient with genetically proven GRA. This study indicates that GRA can cause severe hypertension even in children, associated with an abolished nocturnal BP fall. GRA thus should be excluded in all hypertensive patients with circadian BP rhythm disturbances.
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PMID:Abolished nocturnal blood pressure fall in a boy with glucocorticoid-remediable aldosteronism. 1061 71


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