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2.
Clin Sci (Lond) ; 114(10): 625-34, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17999638

RESUMO

Oxidative stress has been associated with mechanisms of EH (essential hypertension). The aim of the present study was to test the hypothesis that the antioxidant properties of vitamins C and E are associated with a decrease in BP (blood pressure) in patients with EH. A randomized double-blind placebo-controlled clinical trial was conducted in 110 men with grade 1 EH (35-60 years of age without obesity, dyslipidaemia and diabetes mellitus, non-smokers, not undergoing vigorous physical exercise, without the use of any medication and/or high consumption of fruit and vegetables). Participants were randomly assigned to receive either vitamins C+E [vitamin C (1 g/day) plus vitamin E (400 international units/day)] or placebo for 8 weeks. Measurements included 24 h ambulatory BP and blood analysis of oxidative-stress-related parameters in erythrocytes (GSH/GSSH ratio, antioxidant enzymes and malondialdehyde) and plasma [FRAP (ferric reducing ability of plasma)], and levels of 8-isoprostane, vitamins C and E were measured at baseline and after treatment. Following administration of vitamins C+E, patients with EH had significantly lower systolic BP, diastolic BP and mean arterial BP and higher erythrocyte and serum antioxidant capacity compared with either placebo-treated patients with EH or the patients with EH at baseline prior to treatment. BP correlated positively with plasma 8-isoprostane levels and negatively with plasma FRAP levels in the vitamins C+E- and placebo-treated groups. In conclusion, the present study supports the view that oxidative stress is involved in the pathogenesis of EH, and that enhancement of antioxidant status by supplementation with vitamins C and E in patients with EH is associated with lower BP. This suggests intervention with antioxidants as an adjunct therapy for hypertension.


Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Hipertensão/tratamento farmacológico , Vitamina E/uso terapêutico , Vitaminas/uso terapêutico , Adulto , Análise de Variância , Antioxidantes/análise , Ácido Ascórbico/sangue , Determinação da Pressão Arterial , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Método Duplo-Cego , Eritrócitos/metabolismo , Humanos , Hipertensão/sangue , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo , Resultado do Tratamento , Vitamina E/sangue , Vitaminas/sangue
3.
Mol Cell Biochem ; 303(1-2): 73-81, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17410406

RESUMO

Oxidative stress may play a role in the pathogenic mechanism of essential hypertension. Lipid peroxidation can alter the cellular structure of membrane-bound enzymes by changing the membrane phospholipids fatty acids composition. We investigated the relationship between (Na + K)-ATPase activity, lipid peroxidation, and erythrocyte fatty acid composition in essential hypertension. The study included 40 essential hypertensive and 49 healthy normotensive men (ages 35-60 years). Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking, and any current medication. Patients underwent 24-h ambulatory blood pressure monitoring and blood sampling. Lipid peroxidation was measured in the plasma and erythrocytes as 8-isoprostane or malondialdehyde (MDA), respectively. Antioxidant capacity was measured as ferric reducing ability of plasma (FRAP) in the plasma and as reduced/oxidized glutathione (GSH/GSSG ratio) in erythrocytes. (Na + K)-ATPase activity and fatty acids were determined in erythrocyte membranes. Hypertensives had higher levels of plasma 8-isoprostane, erythrocyte MDA, and relative percentage of saturated membrane fatty acids, but lower plasma FRAP levels, erythrocyte GSH/GSSG ratio, (Na + K)-ATPase activity and relative percentage of unsaturated membrane fatty acids, compared with normotensives. Day-time systolic and diastolic blood pressures correlated positively with lipid peroxidation parameters, but negatively with (Na + K)-ATPase activity. These findings suggest that the modulation of (Na + K)-ATPase activity may be associated with changes in the fatty acid composition induced by oxidative stress and provide evidence of a role for this enzyme in the pathophysiology of essential hypertension.


Assuntos
Eritrócitos/metabolismo , Ácidos Graxos/metabolismo , Hipertensão/metabolismo , Peroxidação de Lipídeos , ATPase Trocadora de Sódio-Potássio/metabolismo , Adulto , Monitorização Ambulatorial da Pressão Arterial , Estudos de Casos e Controles , Estudos Transversais , Membrana Eritrocítica/química , Glutationa/metabolismo , Humanos , Hipertensão/patologia , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo
4.
Hypertens Res ; 30(12): 1159-67, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18344620

RESUMO

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/etiologia , Hipertensão/fisiopatologia , Estresse Oxidativo/fisiologia , Adulto , Aldosterona/sangue , Ácido Ascórbico/sangue , Estudos Transversais , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Dinoprosta/urina , Endotelina-1/sangue , Glutationa/sangue , Homocisteína/sangue , Humanos , Hipertensão/sangue , Peroxidação de Lipídeos/fisiologia , Masculino , Pessoa de Meia-Idade , Renina/sangue , Vitamina E/sangue
5.
J Clin Pharmacol ; 43(12): 1299-306, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14615465

RESUMO

The authors examine the available clinical and experimental data supporting the view that homocysteine, an alternative risk factor of cardiovascular disease, may play a role in the pathogenesis of essential hypertension. The mechanism of this disease has not been elucidated, but it may be related to impairment of vascular endothelial and smooth muscle cell function. Therefore, the occurrence of endothelial dysfunction could contribute to alterations of the endothelium-dependent vasomotor regulation. Elevated homocysteinemia diminishes the vasodilation by nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, and alters the elastic properties of the vascular wall. Thus, homocysteine contributes to elevate the blood pressure. Also it is known that elevated plasma levels of homocysteine could lead to oxidant injury to the endothelium. The correction of elevated homocysteinemia by administration of vitamins B12 and B6 plus folic acid, could be a useful adjuvant therapy of hypertension. However, further controlled randomized trials are necessary to establish the efficacy and tolerability of these potentially therapeutic agents.


Assuntos
Antioxidantes/uso terapêutico , Ácido Fólico/uso terapêutico , Homocisteína/metabolismo , Hiper-Homocisteinemia , Hipertensão/etiologia , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/fisiologia , Vitamina B 12/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/fisiopatologia , Hipertensão/prevenção & controle , Óxido Nítrico/antagonistas & inibidores
6.
J Cardiovasc Pharmacol ; 42(4): 453-61, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14508229

RESUMO

The present review examines the clinical and experimental data to support the view that homocysteine and oxidative stress, two alternative risk factors of vascular disease, may play a role in the pathogenesis of primary or essential hypertension. Although the precise mechanism of this disease has not been elucidated, it may be related to impairment of vascular endothelial and smooth muscle cell function. Thus, the occurrence of endothelial dysfunction could contribute to alterations of the endothelium-dependent vasomotor regulation. Hyperhomocysteinemia limits the bioavailability of nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, and alters the elastic properties of the vascular wall. The link between oxidative stress and hyperhomocysteinemia is also biologically plausible, because homocysteine promotes oxidant injury to the endothelium. Cumulated evidence suggests that the diminution of oxidative stress with antioxidants or the correction of hyperhomocysteinemia with vitamins-B plus folic acid, could be useful as an adjuvant therapy for essential hypertension. Further studies involving long-term trials could help to assess the tolerability and efficacy of the use of these therapeutic agents.


Assuntos
Medicina Baseada em Evidências , Homocisteína/sangue , Hipertensão/fisiopatologia , Estresse Oxidativo , Animais , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/fisiopatologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico
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