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

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.
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PMID:Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats. 807 5

Although GRA is said to be one of the least common of the mineralocorticoid-excess states, it is probably underdiagnosed. Moreover, recent advances in our understanding of its pathogenesis has greatly broadened the understanding of this disorder. The development of direct genetic testing for GRA has simplified the diagnostic approach to GRA and will likely increase the detection of many previously undiagnosed cases. Since appropriate treatment can often result in normalization of this refractory form of hypertension, a high index of suspicion should be maintained for this diagnosis when a patient is diagnosed with mineralocorticoid-induced hypertension. It is only through early detection and institution of directed treatment that the morbidity and mortality associated with GRA can be reduced.
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PMID:Glucocorticoid-remediable aldosteronism. 856 22

Monocrotaline (MONO), a pyrrolizidine alkaloid, causes pulmonary arterial hypertension and right ventricular hypertrophy due to hepatic metabolism to the alkylating pyrrole dehydromonocrotaline. Taurine a sulfonic amino acid, is hepato- and cardioprotective in a variety of conditions. We have examined the effects of taurine and its amidino analog, guanidinoethane sulfonate (GES), in rats injected i.p. with MONO (65 mg/kg). Taurine and GES were given as 1% solutions in drinking water beginning 14 days before administration of MONO and continuing for 14 days therafter, when the rats were killed. The MONO group had right ventricular hypertrophy and pulmonary hyperplasia. Compared with control, no significant changes in the right ventricle/left ventricle weight ratio, or the right ventricle/body weight ratio occurred in rats also given taurine of GES. Lung weights in these two groups were higher than in the control group, but below that of the MONO-alone group. The lethality of MONO over 14 days was decreased by taurine (LD50 for MONO alone 80 mg/kg; for MONO + taurine 121 mg/kg). Rats given only MONO had lower hepatic concentrations of GSH and cysteine (Cys), and higher activities of microsomal GSH transferase activity were no different from control. Gamma-Glutamylcysteine (Glu-Cys) synthetase and gamma-glutamyl transpeptidase activities were elevated. In MONO-injected rats given GES, hepatic GSH levels were higher and Cys levels were lower than in either the MONO alone or MONO + taurine groups. Gamma-Glu-Cys synthetase activity was depressed. Microsomal GSH transferase, GSH peroxidase and gamma-glutamyl transpeptidase activities were elevated. Livers of MONO-injected animals showed higher levels of serine (reversed by both taurine and GES) and glycine (Gly; reversed by GES) and lower levels of glutamine. Compared with control rats, the following changes occurred in serum amino acids: MONO alone: increased aspartate, taurine and lysine; taurine-supplemented: increased taurine, methionine (Met) and lysine, and decreased Gly; GES-supplemented: decreased asparagine, serine, Gly, arginine, taurine, and valine. Compared with the MONO-alone group, the taurine-supplemented group had higher glutamate (Glu), Met and alanine, and the GES-supplemented group higher alanine and lower serine, Gly, arginine and valine. We conclude that taurine protects against MONO-induced lethality and right ventricular hypertrophy. GES also protects against right ventricular hypertrophy. However, these agents act by different mechanisms, taurine preventing many of the biochemical changes induced by MONO, with GES inducing additional changes.
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PMID:Effects of taurine and guanidinoethane sulfonate on toxicity of the pyrrolizidine alkaloid monocrotaline. 857 99

Monocrotaline (MONO), a pyrrolizidine alkaloid, causes veno-occlusive disease of the liver, pulmonary arterial hypertension, and right ventricular hypertrophy. Toxicity is due to the hepatic formation of a pyrolic metabolite that can be detoxified by conjugation with glutathione (GSH). We have shown that the GSH content of the liver affects the quantity of the pyrrolic metabolite that is released from the liver. We have now examined whether MONO, in turn, affects GSH metabolism. Twenty-four hours after administration of MONO to rats (65 mg/kg, i.p.), the highest concentration of bound pyrrolic metabolites was found in the liver, followed by the lung and kidney. Heart and brain contained lower concentrations of these metabolites. Significantly higher levels of GSH were found in liver and lungs of MONO-treated rats than in saline-injected control animals. In the liver, activities of the following enzymes were elevated: gamma-glutamylcysteine synthetase, GSH synthetase, gamma-glutamyl transpeptidase, dipeptidase, and microsomal GSH transferase. The same changes were seen in the lung. In the heart, gamma-glutamyl transpeptidase activity was decreased markedly, and cytosolic GSH transferase activity was elevated. In the kidney, the activities of GSH synthetase, gamma-glutamyl transpeptidase, and cytosolic GSH transferase were increased. Our results establish a mutual interaction of MONO and sulfur metabolism. It appears that an early metabolic action of MONO is to modify sulfur amino acid metabolism, diverting cysteine metabolism from oxidation to taurine towards synthesis of GSH.
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PMID:Effects of monocrotaline, a pyrrolizidine alkaloid, on glutathione metabolism in the rat. 857 5

Heart and red blood cell endogenous antioxidant status and plasma lipids were investigated in hypertensive, 14-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Specific heart and red blood cell antioxidant enzyme activities, as well as the susceptibility of tissues to H2O2-induced glutathione (GSH) depletion and lipid peroxidation, were measured. Systolic blood pressure in SHR was greater than in WKY rats at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg (1 mmHg = 133.3 Pa); p < or = 0.05), confirming the presence of hypertension in SHR. Red blood cell catalase (CAT) and superoxide dismutase (SOD) activities were greater (p < or = 0.05) in SHR than WKY rats. Red blood cell CAT activity was positively correlated (r = +0.634; p = 0.026) with SOD, which in turn was correlated (r = +0.709; p = 0.049) with systolic blood pressure. Heart SOD activity was higher (p < or = 0.05) in SHR, while glutathione reductase (GSSG-Red) activity was lower (p < or = 0.05) than in WKY rats. This reduced ability to recycle GSH in the heart coincided with greater (p < or = 0.05) levels of H2O2-induced lipid oxidation products in SHR. Plasma total cholesterol and triacylglycerol levels were lower (p < or = 0.05) in SHR than WKY rats, with no visible signs of atherosclerosis in either SHR or WKY rats. In summary, hypertension in SHR was associated with alterations in antioxidant enzyme profiles of red blood cells and heart, with the latter showing an increased susceptibility to in vitro lipid oxidation. Although hypertension is a recognized factor in the development of human atherosclerosis, spontaneously hypertensive rats did not exhibit signs of aortic plaque, reflecting the resistance of this species to the development of atherosclerosis.
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PMID:Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normotensive Wistar-Kyoto rat. 877 9

1. To determine biochemically the incipient timing of cerebral stroke in stroke-prone spontaneously hypertensive rats (SHRSP) the relation between the glutathione peroxidase (GSH-Px) activity in erythrocytes and the extent of stroke lesion was investigated. 2. When the blood pressure of SHRSP was maintained over 250 mmHg, the GSH-Px activity was lowered and the body weight also decreased. In the SHRSP where the GSH-Px activity in erythrocytes dropped below 23 units/mL blood, the incidence of cerebral stroke was 98% (n = 88/90). 3. The haemoglobin and haematocrit level were unchanged even after the GSH-Px activity dropped to 23 units/mL blood. 4. Lowering of GSH-Px activity in erythrocytes observed during continued hypertension was found to be due to decreased GSH-Px protein, but not to an inactivation of enzymes, as evidenced from immunochemical titration. 5. Lowering of GSH-Px activity in erythrocytes was found to be closely related with the incidence of cerebral stroke in SHRSP. These findings suggest that tracing of the GSH-Px activity in erythrocytes in SHRSP may serve as an indicator for prediction and prognosis of stroke lesion.
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PMID:Relationship between erythrocytes glutathione peroxidase and incidence of stroke lesion in the stroke-prone spontaneously hypertensive rat. 907 38

In 14 patients (4 males and 10 females) with systemic hypertension plasma and erythrocyte lipid peroxides, plasma and erythrocyte catalase activity, plasma glutathione S-transferase (GST) activity, blood reduced glutathione (GSH) content and erythrocyte oxidant stress were investigated. All parameters were performed after clinical examination and then the patients were assigned to receive ACE inhibitor therapy, captopril (25-50 mg given twice per day) or enalapril (10-40 mg given twice per day). After six months the determination of lipid peroxides and antioxidative factors was repeated. At the beginning of the study both treated groups showed significantly higher plasma lipid peroxides compared to the control group. Both used ACE inhibitors produced significant decrease of plasma lipid peroxides after six months. Blood GSH content was also significantly higher in both patient groups before the treatment compared to the controls. Neither captopril nor enalapril produced any significant effect on GSH. Initial values of plasma GST activity in the patients were similar to the control group and did not significantly change after six month treatment. The patients assigned to receive enalapril showed significantly enhanced initial plasma catalase activity according to the controls. After six months treatment both ACE inhibitors significantly decreased plasma catalase activity. Erythrocyte lipid peroxides, erythrocyte catalase activity and oxidant stress of erythrocytes in both groups studied neither differ significantly at initial time of investigation according to the control group nor during or after six month treatment.
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PMID:Changes of lipid peroxides and antioxidative factors levels in blood of patients treated with ACE inhibitors. 912 91

Effects of benidipine hydrochloride or triple therapy (hydralazine, reserpine, and hydrochlorothiazide) on renal cortical and medullary intrinsic antioxidant enzyme (AOE) activity were evaluated in stroke-prone spontaneously hypertensive rats (SHR-SP) as an animal model for human essential hypertension with cerebral stroke. This study showed a significant decrease of renal intrinsic glutathione peroxidase (GSH-Px) activity in untreated SHR-SP. Renal GSH-Px activity in untreated SHR-SP was significantly lower than that in Wister Kyoto rats (WKY) as a normotensive reference strain. GSH-Px activity in SHR-SP was significantly improved after benidipine hydrochloride therapy. Levels of urinary albumin excretion or creatinine clearance (Ccr) in SHR-SP were also improved after the therapy. Glomerular sclerosis index was slightly improved in SHR-SP treated with benidipine hydrochloride according to light microscopic analysis. It appears that hypertension may influence the renal intrinsic GSH-Px activity, albuminuria, and Ccr in SHR-SP. Thus it is indicated that control of blood pressure may improve the GSH-Px activity in SHR-SP.
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PMID:Effects of benidipine hydrochloride on antioxidant enzyme activity in stroke-prone spontaneous hypertensive rats (SHR-SP). 913 5

Glucocorticoid-remediable aldosteronism (GRA) is a rare form of inherited hypertension caused by a characteristic gene duplication. With the advent of definitive genetic testing for GRA, the performance of the traditional screening test for GRA, the dexamethasone suppression test (DST), can be evaluated. We compared the DST to direct genetic testing in 24 patients referred for genetic screening for GRA (12 GRA positive and 12 GRA negative) based on clinical and biochemical findings, DST, and family history. Plasma aldosterone was measured before and after oral dexamethasone administration to determine the extent to which aldosterone was suppressed by glucocorticoids in each patient group. The results of the DST in these subjects were also compared to those in 19 historical patients with primary aldosteronism [4 bilateral hyperplasia and 15 aldosterone-producing adenoma (APA)] reported previously. The DST differentiated GRA-positive from GRA-negative patients with 92% sensitivity and 100% specificity. Cutoffs based on the post-DST plasma aldosterone level (< 4 ng/dL) or percent suppression compared to baseline (> 80%) were equally effective in correctly diagnosing GRA (only one GRA-positive patient would have been incorrectly diagnosed). However, DST in 15 APA patients revealed that 33% had greater than 80% suppression of aldosterone, and 1 had aldosterone levels below 4 ng/dL. We conclued that a post-DST aldosterone level below 4 ng/dL will correctly diagnose GRA patients with high sensitivity and specificity. Suppression compared to baseline can be misleading, as evidenced by the results in APA patients and referred subjects who genetically screened negative.
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PMID:Evaluation of the dexamethasone suppression test for the diagnosis of glucocorticoid-remediable aldosteronism. 936 May 8

In 10 women with disturbed pregnancies without hypertension, reduced (GSH) and oxidized glutathione (GSSG) as well as lipid peroxides as thiobarbituric acid reactive substances (TBARS) were determined in the placenta and in the uterine tissue after unexpected stress-induced Caesarian section (group II). Production of TBARS was also measured in vitro in the 9000 x g supernatant of both tissues. The results were compared with those from women after normal pregnancy and expected Caesarian section (group I). After normal pregnancy higher TBARS and lower GSH with higher GSSG/GSH ratio were found in the placenta in comparison to the uterine tissue, indicating an oxidant/antioxidant imbalance in the placenta. No statistically significant differences were shown between the parameters of groups I and II. The possible oxidant stress associated with disturbed pregnancy and subsequent unexpected Caesarian section in this study was insufficient to alter tissue levels of glutathione nor the peroxidative status of placenta and uterus.
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PMID:Peroxidative and glutathione status in uterus and placenta after normal and pathological pregnancy. 949 53


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