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)

Normal ageing is associated with different changes in the cardiovascular system that lead to an increase in pathological processes such as hypertension and heart failure. Therefore the importance of glutathione peroxidase and catalase for protection against peroxidation was studied in the rat heart. Each of the these enzymes was regulated by feeding rats a low selenium diet either unsupplemented or supplemented with 0.4 parts per million of selenium, with or without the catalase inhibitor, sodium fluoride, in their drinking water. After 2 months, selenium deficient rats had 87% reductions in mitochondrial and cytosolic glutathione peroxidase activities. These reductions were accompanied by increased peroxidation in heart homogenates and mitochondrial suspensions. Since increased mitochondrial peroxidation only occurred when both the cytosolic and mitochondrial glutathione peroxidase activities were involved, these selenoenzymes appear to work in tandem and reductions in both are a prerequisite for increased peroxidation in the heart. Peroxidation did not occur in sodium fluoride treated rats even though cytosolic catalase activity was inhibited by 70%. Moreover, inhibition of catalase activity did not exacerbate the level of peroxidation in selenium deficient rats depleted of glutathione peroxidase activity. Because increased peroxidation was only associated with reductions in glutathione peroxidase activity irrespective of catalase activity, the selenoenzyme appears to be more important for detoxification of hydrogen peroxide in the heart.
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PMID:Enzymatic defenses of the rat heart against lipid peroxidation. 922 21

To determine the effects of vasoactive agents on blood flow in lymph node metastases, the blood flow in the cervical lymph node metastases and normal tissue were meassured using a hydrogen clearance method, at normotensive state, angiotensin I (A I) induced hypertensive state and sodium nitroprusside (SNP) induced hypotensive state. The metastases occurred frequently in the cervical lymph nodes of 17 rats on day 11-14 after Yoshida ascites hepatoma. AH109A cells were subcutaneously inoculated into back of auricule of 20 rats. The blood flow in the liver, brain and bone marrow of normal rats was of no significant changes when the mean arterial blood pressure (MABP) was elevated to approximately 20 kPa by infusion of A I and decreased to approximately 9.06 kPa by infusion of SNP. But the blood flow in the metastatic lymph nodes was increased from 1.42 +/- 0.48 ml.kg-1/s to 3.45 +/- 1.33 ml.kg-1/s (n = 13, P < 0.05) when the MABP was elevated from 14.81 +/- 1.04 kPa to 18.93 +/- 0.92 kPa by A I. On the contrary, the blood flow in the metastatic lymph node was decreased to 0.55 +/- 0.25 ml.kg-1/s (n = 13, P < 0.05) when the MABP was decreased to 8.84 +/- 0.63 kPa by SNP. The results indicated that microcirculation characteristics in the cervical lymph node metastases were different from those in the normal tissues. A I induced hypertension was useful to selectively improve delivery of chemotherapeutic drugs to the site of metastases. On the other hand, SNP induced hypotension may be useful to suppress washout of the drugs.
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PMID:[Establishment of cervical lymph node metastasis in model rats and its microcirculation characteristics]. 938 2

Chronic hypertension is associated with structural and functional changes in the cerebrovascular bed, which influence cerebral circulation and its autoregulation. We examined whether or not long-term treatment of spontaneously hypertensive rats (SHRs) with the new calcium antagonist AE0047 would reverse structural changes in the cerebral vasculature and normalize the elevated lower blood pressure (BP) limit of the cerebral blood flow (CBF) autoregulation. Treating 6-month-old SHRs with a diet containing either 0.013 or 0.04% AE0047 for 8 weeks reduced BP and, at the higher dose, maintained BP at a level similar to that of age-matched Wistar-Kyoto (WKY) rats. At the end of the treatment period, CBF was measured by using the hydrogen-clearance method, and the lower limit of the autoregulation curve was estimated by repeated CBF measurement with stepwise reduction of BP through bleeding. This limit was significantly higher in untreated SHRs than in WKY rats (111 +/- 8 vs. 60 +/- 8 mm Hg). AE0047 caused a significant and dose-dependent shift in the elevated lower BP limit, which decreased to 83 +/- 9 and 75 +/- 6 mm Hg at the low and high dose, respectively. In perfusion-fixed proximal, intermediate, and distal portions of the middle cerebral artery, media thickness/external diameter (M/ED) ratios were significantly greater in untreated SHRs than in WKY rats. In AE0047-treated animals, M/ED ratios in all portions tended to be reduced halfway between those for untreated SHRs and those for WKY rats, but with no statistical significance. These results suggest that long-term treatment of patients with hypertension with AE0047 will normalize the autoregulatory threshold while preserving CBF and thereby improve tolerance to BP reduction, but the potential to ameliorate structural alterations may be small.
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PMID:Effects of long-term treatment with the calcium antagonist AE0047 on cerebrovascular autoregulation and hypertrophy in spontaneously hypertensive rats. 938 44

Enhanced production of oxygen free radicals may play a role in hypertension by affecting vascular smooth muscle contraction, resistance to blood flow, and organ damage. The aim of this study was to determine whether oxygen free radicals are involved in the development of salt-induced hypertension. Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed either a high salt (6.0% NaCl) or low salt (0.3% NaCl) diet for 4 weeks. The high salt diet caused the development of severe hypertension in Dahl-S animals and had no effect on blood pressure in Dahl-R animals. A tetranitroblue tetrazolium dye was used to detect superoxide radicals in microvessels of the mesentery. Light absorption measurements revealed enhanced staining along the endothelium of arterioles and venules in hypertensive Dahl-S animals, with significantly lower values in normotensive animals. In addition, a Clark electrochemical electrode was used to measure hydrogen peroxide levels in fresh plasma. Hypertensive Dahl-S animals had a higher plasma hydrogen peroxide concentration compared with their normotensive counterparts (2.81+/-0.43 versus 2.10+/-0.41 micromol/L), while no difference was detected between high- and low salt-treated Dahl-R animals (1.70+/-0.35 versus 1.56+/-0.51 micromol/L). The plasma hydrogen peroxide levels of all groups correlated with mean arterial pressure (r=.77). These findings demonstrate an enhanced production of oxygen free radicals in the microvasculature of hypertensive Dahl-S rats.
Hypertension 1997 Dec
PMID:Oxidative stress in the Dahl hypertensive rat. 940 93

Both endothelial cells and vascular smooth muscle cells are capable of producing reactive oxygen species from a variety of enzymatic sources. In disease states such as atherosclerosis and hypertension, vascular production of these reactive oxygen metabolites can increase substantially. Increases in the production of superoxide anion can lead to decreases in ambient levels of nitric oxide via a facile radical/radical reaction that occurs more rapidly than the reaction of superoxide anion with superoxide dismutase. This phenomenon alters endothelial regulation of vasomotion in a variety of disease conditions. Recent evidence suggests that the major source of vascular superoxide ion and hydrogen peroxide is a membrane-bound, reduced nicotinamide-adenine dinucleotide (NADH)-dependent oxidase. The activity of this enzyme system is regulated by angiotensin II and is elevated following prolonged exposure to nitroglycerin. Alterations of vascular oxidant state caused by angiotensin II may contribute substantially to vascular pathology and may also provide a link between hypertension and atherosclerosis.
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PMID:Endothelial function and oxidant stress. 942 47

1. Pregnancy is associated with a 30-50% rise in cardiac output and a 50% increase in blood volume. The contribution of changes in the activity of primary and secondary active transporters to these haemodynamic adaptations remains unknown. For the first time, we measured sodium-hydrogen exchange activity over the course of normal pregnancy. 2. Eighteen healthy pregnant women were studied at 14, 24 and 33 weeks of gestation and compared with 18 non-pregnant healthy women. None of the pregnancies was complicated by hypertension. At each antenatal visit, body weight and blood pressure were recorded, blood and 24 h-urine samples were taken to control renal function and metabolic equilibrium, maternal glucose tolerance was evaluated by oral glucose test and glycated haemoglobin testing, and erythrocyte sodium-hydrogen antiport was also measured. 3. Erythrocyte antiport activity values were 10.0 +/- 3.0, 9.6 +/- 2.9 and 8.4 +/- 3.5 mmol h-1 (litre of cells)-1 in the three gestational trimesters respectively, significantly higher at each trimester than in control women [6.8 +/- 2.5 mmol h-1 (litre of cells)-1]. The clearances of urea and creatinine were constantly elevated in pregnant women; at each trimester their serum concentrations were lower than in non-pregnant women. Serum potassium significantly decreased during pregnancy. Serum total cholesterol and triacylglycerol levels, already above the normal range from the first trimester, further increased until the third trimester. The area under the glycaemic curve became larger during pregnancy, and the area under the insulinaemic curve increased to a lesser extent. There was a significant association between antiport activity and serum triacylglycerol levels. 4. The observed hyperactivity of the transporter, peaking at the fourteenth week of gestation, may be a contributing factor to the haemodynamic adjustments attending upon normal pregnancy.
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PMID:Activity of erythrocyte sodium-hydrogen exchange in normal pregnancy. 948 88

Diabetic nephropathy develops in a subset of patients with an apparently hereditary predisposition. Microalbuminuria and elevated arterial pressure have been proposed as predictors of nephropathy but both appear when renal damage is impending. Enhanced sodium-hydrogen exchange in the cell membranes of diabetic patients is an early marker of diabetic nephropathy but its predictive value has not been assessed. In this study, sodium-hydrogen exchange was measured in erythrocytes as an initial velocity of amiloride-inhibited H+ efflux (pH 6.35-6.45) into a Na+ - containing medium (pH 7.95-8.05) in 156 non-microalbuminuric insulin-treated diabetic patients (98 women, 58 men, age 33+/-8 years, diabetes duration prior to enrollment 15+/-4 years) during 8 years of follow-up. Enhanced erythrocyte sodium-hydrogen exchange predicted diabetic nephropathy alone and in association with a familial tendency to hypertension/nephropathy with 86 and 96% sensitivity, and 80% specificity. Thus, sodium-hydrogen exchange appears to detect a subset of diabetic patients prone to develop renal damage, in whom a more intensive treatment modality might be considered.
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PMID:Enhanced erythrocyte Na+/H+ exchange predicts diabetic nephropathy in patients with IDDM. 949 54

Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H4B) may generate damaging superoxide (O2-). This study was designed to determine whether cNOS-dependent generation of O2- occurs in spontaneously hypertensive rats (SHR) before the onset of hypertension. Aortas from 4-wk-old SHR and Wistar-Kyoto rats were used. cNOS was stimulated by calcium ionophore A23187. In situ measurements of nitric oxide and hydrogen peroxide by electrochemical sensors and O2- production by chemiluminescence method were performed. Isometric tension was continuously recorded. H4B by high performance liquid chromatography and [3H]citrulline assay were determined in homogenized tissue. The A23187-stimulated production of O2- and its superoxide dismutase product hydrogen peroxide were significantly higher, whereas nitric oxide release was reduced in SHR aortas, with opposite results in the presence of exogenous H4B. Furthermore, NG-monomethyl-L-arginine inhibited the generation of cNOS-dependent O2- by approximately 70%. Natural H4B levels were similar in both strains; however, equivalent cNOS activity required additional H4B in SHR. The endothelium-dependent relaxations to A23187 were significantly inhibited by catalase, and enhanced by superoxide dismutase, only in SHR; however, these enzymes had no effect in the presence of H4B. Thus, dysfunctional cNOS may be a source of O2- in prehypertensive SHR and contribute to the development of hypertension and its vascular complications.
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PMID:Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. 952 96

Acute hypertension provokes a rapid decrease in proximal tubule sodium reabsorption with a decrease in basolateral membrane sodium-potassium-ATPase activity and an increase in the density of membranes containing apical membrane sodium/hydrogen exchangers (NHE3) [Y. Zhang, A. K. Mircheff, C. B. Hensley, C. E. Magyar, D. G. Warnock, R. Chambrey, K.-P. Yip, D. J. Marsh, N.-H. Holstein-Rathlou, and A. A. McDonough. Am. J. Physiol. 270 (Renal Fluid Electrolyte Physiol. 39): F1004-F1014, 1996]. To determine the reversibility and specificity of these responses, rats were subjected to 1) elevation of blood pressure (BP) of 50 mmHg for 5 min, 2) restoration of normotension after the first protocol, or 3) sham operation. Systolic hypertension increased urine output and endogenous lithium clearance three- to fivefold within 5 min, but these returned to basal levels only 15 min after BP was restored. Renal cortex lysate was fractionated on sorbitol gradients. Basolateral membrane sodium-potassium-ATPase activity (but not subunit immunoreactivity) decreased one-third to one-half after BP was elevated and recovered after BP was normalized. After BP was elevated, 55% of the apical NHE3 immunoreactivity, smaller fractions of sodium-phosphate cotransporter immunoreactivity, and apical alkaline phosphatase and dipeptidyl-peptidase redistributed to membranes of higher density enriched in markers of the intermicrovillar cleft (megalin) and endosomes (Rab 4 and Rab 5), whereas density distributions of the apical cytoskeleton protein villin were unaltered. After 20 min of normalized BP, all the NHE3 and smaller fractions of the other apical membrane proteins returned to their original distributions. These findings suggest that the dynamic regulation of proximal tubule sodium transport by acute changes in BP may be mediated by rapid reversible regulation of sodium pump activity and relocation of apical sodium transporters.
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PMID:Reversible effects of acute hypertension on proximal tubule sodium transporters. 957 7

Increased production of oxygen free radicals may play a role in many diseases such as hypertension. As evidence indicates that xanthine oxidase may be involved in creating these reactive oxygen species, experiments were performed to additionally characterize hydrogen peroxide (H2O2) production in xanthine oxidase catalyzed reactions. In vitro measurements of hydrogen peroxide production from the xanthine/xanthine oxidase reaction were performed in buffered saline using an electrochemical technique, and the effect of allopurinol on inhibition of xanthine oxidase was determined. Experiments were also performed in blood plasma to characterize endogenous hydrogen peroxide producing capability and xanthine oxidase activity. In the presence of sodium azide, an inhibitor of catalase, peroxide production was measured in plasma after adding xanthine or xanthine oxidase and the results were similar to those obtained in buffered saline. When only sodium azide was added to plasma, hydrogen peroxide was produced at a level of 36.1 +/- 7.6 microM (n = 5). From these measurements, endogenous xanthine oxidase activity was estimated to be 6.5 +/- 0.3 mU/ml (n = 5). These results suggests that sufficient substrate exists in plasma to produce micromolar levels of hydrogen peroxide and xanthine oxidase may catalyze these reactions.
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PMID:Role of xanthine oxidase in hydrogen peroxide production. 980 Oct 73


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