Sex differences in oxidative stress and the impact on blood pressure control and cardiovascular disease

Clin Exp Pharmacol Physiol. 2007 Sep;34(9):938-45. doi: 10.1111/j.1440-1681.2007.04643.x.

Abstract

1. In the present review, we addressed studies in humans and rats to determine the role that oxidative stress may play in mediating cardiovascular outcomes. 2. Biochemical evaluation of oxidative stress in both humans and spontaneously hypertensive rats gives equivocal results as to the relative levels in males versus females. Clinical trials with anti-oxidants in humans have not shown consistent results in protecting against detrimental cardiovascular outcomes. In spontaneously hypertensive rats (SHR), blockade studies using tempol or apocynin reduce renal oxidative stress and blood pressure in male SHR, but not in female rats. In addition, increasing oxidative stress with molsidomine increases blood pressure in male, but not female, SHR. Treatment with vitamins E and C reduces blood pressure in young male, but not aged, animals. Furthermore tempol is unable to reduce blood pressure in young male SHR in the absence of a functional nitric oxide system. 3. Neither human nor animal studies are consistent in terms of whether oxidative stress levels are higher in males or females. Furthermore, anti-oxidant therapy in humans often does not ameliorate, or even attenuate, the negative cardiovascular consequences of increased oxidative stress. Our studies in SHR shed light on why these outcomes occur.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetophenones / pharmacology
  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Ascorbic Acid / pharmacology
  • Blood Pressure / drug effects*
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control
  • Catalase / metabolism
  • Cyclic N-Oxides / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glutathione Peroxidase / metabolism
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Kidney / drug effects*
  • Kidney / enzymology
  • Kidney / metabolism
  • Male
  • Molsidomine / pharmacology
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Inbred SHR
  • Sex Factors
  • Spin Labels
  • Superoxide Dismutase / metabolism
  • Vitamin E / pharmacology

Substances

  • Acetophenones
  • Antioxidants
  • Cyclic N-Oxides
  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Spin Labels
  • Vitamin E
  • Nitric Oxide
  • acetovanillone
  • Molsidomine
  • Catalase
  • Glutathione Peroxidase
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • NADPH Oxidases
  • Ascorbic Acid
  • tempol
  • NG-Nitroarginine Methyl Ester