Oxidative stress in human hypertension: association with antihypertensive treatment, gender, nutrition, and lifestyle

https://doi.org/10.1016/j.freeradbiomed.2003.10.021Get rights and content

Abstract

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension. Our aim was to measure markers of oxidative stress in hypertensive subjects, and assess the potential confounding influences of antihypertensive therapy, other cardiovascular risk factors, gender, lifestyle, and nutrition. Markers of oxidative stress, including plasma and 24 h urinary F2-isoprostanes, were measured in 70 untreated (men = 43, women = 27) and 85 treated (men = 43, women = 42) hypertensive subjects and 40 normotensive controls (men = 20, women = 20). Overall, F2-isoprostanes were not elevated in hypertensive subjects compared with controls. However, urinary and plasma F2-isoprostanes were significantly lower in treated compared with untreated hypertensive men, but not women. In hypertensive men, the number of antihypertensive drugs taken was inversely associated with both urinary and plasma F2-isoprostanes (p < .05). Self-reported alcohol intake and biomarkers of alcohol consumption (γ-glutamyl transpeptidase and high-density lipoprotein cholesterol) were positively associated with plasma but not urinary, F2-isoprostanes in men. Several nutrients were independently associated with plasma and urinary F2-isoprostanes in women. The results do not support the hypothesis that treated or untreated hypertensive subjects are under increased oxidative stress compared with normotensive controls.

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.

Section snippets

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.

References (38)

  • S.R. Thomas et al.

    Molecular action of vitamin E in lipoprotein oxidation: implications for atherosclerosis

    Free Radic. Biol. Med.

    (2000)
  • F.J. Nieto et al.

    Uric acid and serum antioxidant capacity: a reaction to atherosclerosis?

    Atherosclerosis

    (2000)
  • K.V. Kumar et al.

    Are free radicals involved in the pathobiology of human essential hypertension?

    Free Radic. Res. Commun.

    (1993)
  • F. Lacy et al.

    Plasma hydrogen peroxide production in human essential hypertension: role of heredity, gender and ethnicity

    Hypertension

    (2000)
  • G. Zalba et al.

    Oxidative stress in arterial hypertension: role of NAD(P)H oxidase

    Hypertension

    (2001)
  • A. Makino et al.

    Increased renal medullary oxidative stress produces hypertension

    Hypertension

    (2002)
  • J. Pedro-Botet et al.

    Decreased endogenous antioxidant enzymatic status in essential hypertension

    J. Hum. Hypertens.

    (2000)
  • T. Ide et al.

    Greater oxidative stress in healthy young men compared with premenopausal women

    Arterioscler. Thromb. Vasc. Biol.

    (2002)
  • G. Block et al.

    Factors associated with oxidative stress in human populations

    Am. J. Epidemiol.

    (2002)
  • Cited by (129)

    • Role of oxidative stress in the pathogenesis of metabolic syndrome

      2023, Metabolic Syndrome: From Mechanisms to Interventions
    • Increased nitro-oxidative stress toxicity as a major determinant of increased blood pressure in mood disorders

      2021, Journal of Affective Disorders
      Citation Excerpt :

      Decreased levels of vitamins A, C, and E and biomarkers of oxidative stress are associated with (untreated) hypertension (Montezano et al., 2015; Montezano and Touyz, 2014; Ward et al., 2004). In patients with essential hypertension, systolic and diastolic blood pressure assessments correlate positively with endothelial dysfunction in association with increased vascular ROS production, oxidative stress toxicity, and vascular inflammation (Ahmad et al., 2013; Carrizzo et al., 2013; Ward et al., 2004). Approximately 30% of subjects with a diagnosis of hypertension show indicants of insulin resistance (Gupta et al., 2019; Ormazabal et al., 2018) and depressed people have a 37%–60% increased risk of developing diabetes (Fugger et al., 2019; Yu et al., 2015).

    • Oxidative Stress: A Unifying Paradigm in Hypertension

      2020, Canadian Journal of Cardiology
    • Oxidative stress and hypertension in old age: The role of physical exercise

      2020, Aging: Oxidative Stress and Dietary Antioxidants
    View all citing articles on Scopus
    View full text