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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glutathione (GSH) system plays an important role in reducing oxidative stress, the increase of which has been linked to the pathogenesis of hypertension. The aims of this study were to investigate: (1) whether the GSH system was impaired in aortic smooth muscle cells (SMCs) from spontaneously hypertensive rats (SHR), and (2) whether this system could be up-regulated by the phase-2 enzyme inducers, sulforaphane and t-butylhydroquinone (t-BHQ). Basal levels of cellular GSH, GSH-reductase and GSH-peroxidase were significantly lower in SMCs from SHR than from normotensive Wistar-Kyoto (WKY) rats. Heme oxygenase-1 (HO-1) was significantly higher in SHR SMCs, which correlated with the higher oxidative stress experienced by these cells. No differences were observed in the basal activity of GSH-S-transferase nor in the ability to synthesize GSH between SMCs from these two strains. Sulforaphane (0.05-1 micromol/l) and t-BHQ (10-100 micromol/l) induced significant and concentration-dependent increases in cellular GSH levels, HO-1 protein content and activities of GSH-reductase and GSH-peroxidase in SMCs from both rat strains. Upregulation of phase 2 enzymes correlated with a decrease in oxidative stress experienced by the SMCs, particularly with SHR. We conclude that SHR SMCs experience greater oxidative stress than WKY SMCs and that malfunction of the GSH system contributes to the enhanced oxidative stress in SHR SMCs.
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PMID:The impaired glutathione system and its up-regulation by sulforaphane in vascular smooth muscle cells from spontaneously hypertensive rats. 1159 2

Induction of chronic oxidative stress by glutathione (GSH) depletion has been shown to cause hypertension in normal rats. This was accompanied by and perhaps in part due to inactivation and sequestration of NO by reactive oxygen species (ROS), leading to diminished NO bioavailability. This study was designed to examine renal histology, nitric oxide synthase (NOS) isotype expression, and nitrotyrosine distribution in this model. Sprague-Dawley rats were subjected to oxidative stress by administration of the GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mM/l in drinking water) for 2 weeks. The controls were given tap water. Blood pressure, renal histology, tissue expression of endothelial and inducible NOS (eNOS and iNOS) and nitrotyrosine, tissue GSH content, and urinary excretion of NO metabolites (NOx) were examined. The BSO-treated group showed a 3-fold decrease in tissue GSH content, a marked elevation in blood pressure, and a significant reduction in the urinary excretion of NOx. Histological examination of kidneys revealed no significant abnormalities in either group. In addition, no significant differences were observed in either intensities or localizations of eNOS and iNOS in the kidney. However, the BSO-treated group exhibited intense accumulation in the renal tissue of nitrotyrosine, which is the footprint of NO oxidation by ROS. These observations suggest that oxidative stress-induced hypertension is not caused by either structural abnormality of or depressed NOS expression by the kidney in this model. Instead, it is associated with and perhaps partially related to enhanced renal NO inactivation by ROS and diminished NO bioavailability.
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PMID:Nitric oxide synthase expression in hypertension induced by inhibition of glutathione synthase. 1186 79

Monogenic or Mendelian forms of hypertension have ushered in a revolution in our knowledge. If we add information on syndromes involving low blood pressure, this knowledge base is doubled. Glucocorticoid-remediable aldosteronism, apparent mineralocorticoid excess, and mutations in the mineralocorticoid receptor gene have given us brilliant insights into mineralocorticoid-induced hypertension. The latter discovery has elucidated how mutations may modify the receptor sufficiently to allow erstwhile antagonists to have an agonistic action. The epithelial sodium channel (ENaC) has been elucidated. Gain-of-function mutations in the beta and gamma subunits of ENaC cause Liddle's syndrome. Loss-of-function mutations in all 3 subunits of ENaC cause hypotension (pseudohypoaldosteronism type I). Thus, all 3 subunits can be mutated, causing either hyper- or hypotension. Three loci have been described for Gordon's syndrome, pseudohypoaldosteronism type II; 2 members of the WNK (with no ly sine K) serine-threonine kinase family have recently been found to be responsible. Autosomal-dominant hypertension with brachydactyly features normal sodium and renin-angiotensin-aldosterone responses. The gene has been mapped to chromosome 12p. The condition is interesting because it may represent a novel neural form of hypertension. The elucidation of Mendelian blood pressure-regulatory disorders has been a resounding success.
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PMID:Monogenic forms of human hypertension. 1189 1

Hypertension and coronary artery disease are intimately connected. The migration of circulating monocytes into the subendothelial occurs through the expression of some adhesion molecules on endothelial cells. The nuclear factor (NF)-kappaB, a redox-sensitive element, plays a key role in adhesion molecule gene induction. In this study we have compared the effects of two different angiotensin converting enzyme (ACE) inhibitors, one possessing an active sulfhydryl group (zofenopril) and one lacking this group (enalapril) on the cellular redox state (monitored by measuring intracellular reactive oxygen species and thiol status), expression of adhesion molecules, and activation of NF-kappaB in human umbilical vein endothelial cells (HUVECs). Zofenoprilat, the active form of zofenopril, significantly and dose dependently reduced the intracellular reactive oxygen species (ROS) and superoxide formation induced by oxidized low-density lipoprotein (ox-LDL) (P <.001) and tumor necrosis factor-alpha (TNF-alpha) (P <.001). Enalaprilat, the active form of enalapril, was ineffective. Zofenoprilat but not enalaprilat also decreased the consumption of the intracellular GSH induced by ox-LDL (P <.01) and TNF-alpha (P <.01). Although zofenoprilat significantly and dose dependently reduced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and E-selectin induced by ox-LDL (P <.01) and TNF-alpha (P <.01) on HUVECs, enalaprilat did not. Ox-LDL and TNF-alpha increased the activation of NF-kappaB and the preincubation of HUVECs with zofenoprilat, but not with enalaprilat, dose dependently reduced its activation (P <.001). The conclusion is that the sulfhydryl (SH)-containing ACE inhibitors may be useful in inhibiting foam cell formation and thus slow the development of atherosclerosis.
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PMID:Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species. 1237 76

Aldosterone, the major circulating mineralocorticoid, particiates in blood volume and serum potassium homeostasis. Primary aldosteronism is a disorder characterized by hypertension and, in more severe form, hypokalemia, due to autonomous aldosterone secretion from the adrenocortical zona glomerulosa. Improved screening techniques, particularly application of the plasma aldosterone: plasma renin activity ratio, has led to renewed interest in Conn's original proposal that primary aldosteronism may be the cause of increased blood pressure in about 10% of adults with hypertension. Glucocorticoid-remediable aldosteronism (GRA) was the first described familial form of hyperaldosteronism. The disorder is characterized by aldosterone secretory function regulated chronically by ACTH. Hence, aldosterone hypersecretion can be chronically suppressed by exogenous glucocorticoids such as dexamethasone in physiologic-range doses. This autosomal dominant disorder has been shown to be caused by a hybrid gene mutation formed by a cross-over of genetic material between the ACTH-responsive regulatory portion of the 11b-hydroxylase (CYP11B1) gene and the coding region of the aldosterone synthase (CYP11B2) gene. Familial hyperaldosteronism type II (FH-II), so named to distinguish the disorder from GRA or familial hyperaldosteronism type I (FH-I), is characterized by inheritance consistent with an autosomal dominant pattern of autonomous aldosterone hypersecretion which is not suppressible by dexamethasone. Linkage analysis in a single large kindred, and direct mutation screening, has shown that this disorder is unrelated to mutations in the genes for aldosterone synthase or the angiotensin II receptor. A recent genome-wide search has identified a genetic linkage between FH-II in this single large kindred and polymorphic gene markers on chromosome 7 in a region that corresponds to cytogenetic band 7p22. This is the first identified locus for FH-II. Several possible candidate genes have been localized to the 7p22 region. The precise genetic cause of FH-II remains to be elucidated.
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PMID:New genetic insights in familial hyperaldosteronism. 1238 43

Nitric oxide (NO) has a role in the etiopathogenesis of hypertension. Relaxation of vascular smooth muscles is failed when NO production is reduced leading to increased vascular peripheral resistance. N sup omega nitro-L-arginine methyl ester (L-NAME) is one of the inhibitors of NO production. The aim of this study was to investigate oxidant-antioxidant systems of renal tissue in rats with hypertension induced by L-NAME. Rats were divided into three groups: control group and study groups treated with 100 or 500 mg/l L-NAME in drinking water for 15 days. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and NO were studied in the renal tissue after hypertension induction. Arterial blood pressure was increased in both L- NAME groups. CAT activity of 500-mg L-NAME group was higher than control. GSH-Px activity of 500-mg L-NAME group was decreased compared with 100-mg ones. NO level was lower in 500-mg L-NAME group than control. MDA levels in both L-NAME groups were decreased compared with control. In conclusion, hypertension was induced with oral L-NAME treatment. Increased CAT activity was compensated with decreased GSH-Px activity in 500-mg L-NAME group. Both study groups were protected from lipid peroxidation with NO inhibition.
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PMID:Renal antioxidant status in rats with hypertension induced by N sup omega nitro-L-arginine methyl ester. 1242 22

The present study was designed to determine whether changes in dietary protein source are related to changes in antioxidant status determined by enzyme activities of catalase, superoxide dismutase (SOD), gluthatione peroxidase (GSH-Px) and gluthatione reductase (GSSG-Red) and lipid peroxidation levels in various tissues. Spontaneously hypertensive rats (SHR; 5 wk old) were fed diets containing 20% casein or fish protein for 2 mo. Feeding the fish protein diet lowered blood pressure and reduced plasma total cholesterol levels and SOD activity in all tissues except muscle compared with the casein diet. Feeding fish protein also enhanced GSH level and GSH-Px activity in liver and heart, accompanied by lower lipid peroxidation. In kidney, however, the lower catalase activity in rats fed fish protein was associated with an enhancement in lipid peroxidation. Plasma and VLDL + LDL lipid peroxidation was unaffected by dietary proteins. In conclusion, the fish protein diet did not play a relevant role in plasma antioxidative defense status but increased it in liver and heart compared with the casein diet. Fish protein attenuated the development of hypertension and also decreased plasma total cholesterol concentration. Thus, it enhances protection against cardiovascular diseases.
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PMID:Tissue antioxidant status differs in spontaneously hypertensive rats fed fish protein or casein. 1256 87

A positive family history of coronary heart disease (CHD) is one of the most predictive risk factors of CHD. Many children with increased risk of CHD because of their positive family history of CHD do not present other risk factors, such as altered serum lipid profile. Oxidative stress plays an important part in the pathogenesis of atherosclerosis. Serum antioxidants and intracellular enzymatic antioxidants composed mainly of glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase counterbalance oxidative stress. Diminished activity of this system may lead to accelerated progression of atherosclerosis. The aim of this study was to assess the activity of CAT, GSH-Px, SOD and glutathione reductase in children with a family history of premature CHD who did not present any other major risk factors of CHD (diabetes, obesity, dyslipidaemia or hypertension). Twenty-two healthy children from high-risk families, selected according to the National Cholesterol Education Program definition, were enrolled in the study. The control group comprised 18 children without a family history of CHD. All the children were healthy and had been screened for hyperlipidaemia, diabetes, hypertension and obesity prior to the study. The erythrocyte activity of CAT, GSH-Px, SOD and glutathione reductase was assessed. Children at high risk of CHD had a statistically significant lower level of GSH-Px and CAT activity than the children in the control group. There were no statistically significant differences in the activity of SOD and glutathione reductase.
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PMID:Activity of antioxidant enzymes in children from families at high risk of premature coronary heart disease. 1275 97

The study investigated whether the amelioration of endothelial dysfunction by candesartan (2 mg.kg-1.day-1; 10 wk) in spontaneously hypertensive rats (SHR) was associated with modification of hepatic redox system. Systolic arterial pressure (SAP) was higher (P < 0.05) in SHR than in Wistar-Kyoto rats (WKY) and was reduced (P < 0.05) by candesartan in both strains. Acetylcholine (ACh) relaxations were smaller (P < 0.05) and contractions induced by ACh + NG-nitro-l-arginine methyl ester (l-NAME) were greater (P < 0.05) in SHR than in WKY. Treatment with candesartan enhanced (P < 0.05) ACh relaxations in SHR and reduced (P < 0.05) ACh + l-NAME contractions in both strains. Expression of aortic endothelial nitric oxide synthase (eNOS) mRNA was similar in WKY and SHR, and candesartan increased (P < 0.05) it in both strains. Aortic mRNA expression of the subunit p22phox of NAD(P)H oxidase was higher (P < 0.05) in SHR than in WKY. Treatment with candesartan reduced (P < 0.05) p22phox expression only in SHR. Malonyl dialdehyde (MDA) levels were higher (P < 0.05), and the ratio reduced/oxidized glutathione (GSH/GSSG) as well as glutathione peroxidase activity (GPx) were lower (P < 0.05) in liver homogenates from SHR than from WKY. Candesartan reduced (P < 0.05) MDA and increased (P < 0.05) GSH/GSSG ratio without affecting GPx. Vessel, lumen, and media areas were bigger (P < 0.05) in SHR than in WKY. Candesartan treatment reduced (P < 0.05) media area in SHR without affecting vessel or lumen area. The results suggest that hypertension is not only associated with elevation of vascular superoxide anions but with alterations of the hepatic redox system, where ANG II is clearly involved. The results further support the key role of ANG II via AT1 receptors for the functional and structural vascular alterations produced by hypertension.
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PMID:Effect of AT1 receptor blockade on hepatic redox status in SHR: possible relevance for endothelial function? 1277 56

The suggested involvement of ouabain in hypertension raised the need for a better understanding of its cellular action, but the mechanisms of ouabain toxicity are only now being uncovered. In the present study, we show that reduced glutathione (GSH) protected ouabain-sensitive (OS) cells from ouabain-induced toxicity and that the inhibition of GSH synthesis by D, L-buthionine-(S,R)-sulfoximine (BSO) sensitized ouabain-resistant (OR) cells. We could not observe formation of *OH or H2O2, but there was an increase in O2*-only in OS cells. Unexpectedly, an increased number of OR cells depolarized after treatment with ouabain, and BSO blocked this depolarization. Moreover, GSH increased ouabain-induced depolarization in OS cells. A sustained increase in tyrosine phosphorylation (P-Tyr) and Ras expression was observed after treatment of OS cells, and GSH prevented it. Conversely, BSO induced P-Tyr and Ras expression in ouabain-treated OR cells. The results obtained have three major implications: There is no direct correlation between membrane depolarization and ouabain-induced cell death; ouabain toxicity is not directly related to its classical action as a Na+, K+-ATPase inhibitor but seems to be associated to signal transduction, and GSH plays a major role in preventing ouabain-induced cell death.
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PMID:Mechanisms of ouabain toxicity. 1295 81


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