Oxidative stress in human hypertension: association with antihypertensive treatment, gender, nutrition, and lifestyle
Introduction
Oxidative stress is thought to play a critical role in the pathogenesis of hypertension. The precise mechanisms remain to be elucidated [1], [2], [3], [4]. However, there is general consensus that reactive oxygen species (ROS) play a role, mediating oxidative damage to target organs, decreasing nitric oxide bioavailability, and giving rise to endothelial dysfunction [5].
Evidence that hypertension is a state of oxidative stress derives from a range of sources. Elevated levels of superoxide, hydrogen peroxide, and lipid peroxides and decreased superoxide dismutase (SOD) and vitamin E have been observed in hypertensive subjects compared with normotensive controls [1]. An elevated level of plasma hydrogen peroxide production has been observed in hypertensive compared with normotensive subjects, and there was a significant relationship between plasma hydrogen peroxide production and blood pressure (BP) [2]. Untreated hypertensive subjects were found to have significantly lower erythrocyte SOD and whole blood glutathione peroxidase (GPx) activity compared with to controls [6], [7], [8]. Higher levels of malondialdehyde (MDA) and lipid peroxides and reduced total antioxidant capacity have also been measured in untreated hypertensive subjects compared with normotensive controls [9]. In contrast, two recent studies involving small numbers, one in treated hypertensive subjects [10] and another in untreated mild-to-moderate hypertensive subjects [11], found no difference in urinary isoprostanes in comparison to normotensive control subjects. The F2-isoprostanes, prostaglandin-like products formed by free radical peroxidation of arachidonic acid in membranes, represent a reliable and specific in vivo marker of lipid peroxidation [12].
Our objective in this study was to investigate the hypothesis that hypertension is associated with increased oxidative stress with careful evaluation of the potential confounding influences of antihypertensive therapy, other cardiovascular risk factors, gender, nutrition, and lifestyle factors. We have therefore examined markers of oxidative stress including urinary and plasma F2-isoprostanes, total antioxidant capacity, and plasma vitamin E and C levels in treated and untreated hypertensive subjects and normotensive control subjects.
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Subjects
Between October 2000 and December 2001, 155 hypertensive subjects and 40 normotensive control subjects were recruited from the Perth general population to the Royal Perth Hospital Unit of the School of Medicine and Pharmacology at the University of Western Australia. All volunteers ceased any vitamin, antioxidant, or fish oil supplements for a minimum of 4 weeks prior to entry into the study. Where possible, all prescribed medications were taken as normal on the morning of each visit. Exclusion
Results
Table 1 outlines the characteristics of the untreated hypertensive subjects, treated hypertensive subjects, and normotensive controls. The treated hypertensive subjects were significantly older than the untreated hypertensive subjects and normotensive controls. Mean 24 h systolic and diastolic BP reflected expected differences between untreated and treated hypertensive subjects and controls. Of the 85 treated hypertensive subjects, 65% were on one, 27% on two, 4% on three, and 4% on four
Discussion
In this study we observed no significant difference in markers of oxidative stress between hypertensive subjects and normotensive control subjects. This is in agreement with previous studies, which found no differences in urinary F2-isoprostanes [10], [11], but in contrast to studies using nonspecific markers of oxidative damage [9]. This variation in findings may relate to differences in methodologies for the assessment of oxidative stress. Treated hypertensive men had significantly lower F2
Acknowledgements
This study was funded by the National Health and Medical Research Council of Australia (NHMRC) under Grant 139067. N.C.W. acknowledges the assistance of a University of Western Australia Postgraduate Award. The authors thank the volunteers who took part in the study and Jennifer Rivera for technical assistance.
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