Sex Differences in Oxidative Stress and the Impact on Blood Pressure Control and Cardiovascular Disease

Abstract

SUMMARY1. 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.

Sex differences in control of blood pressure: role of oxidative stress in hypertension in females

“…However, in contrast to young adult males, vitamins E and C failed to reduce blood pressure significantly in old male SHR, although urinary F 2 -isoprostanes were reduced. As mentioned previously, in young adult female SHR, 6-wk treatment with vitamins E and C failed to have an effect on oxidative stress but reduced blood pressure (56). Tempol had no effect on either oxidative stress or blood pressure in young females.…”

Sex Steroids and Renal Disease

“…86 Renal antioxidant enzyme expression is higher in male SHR than in females. 85 However, unlike in male WKY rats, male SHR fail to upregulate renal expression of antioxidant enzymes when oxidative stress is increased with molsidomine. 85 Whether oxidative stress is higher in male or female SHR is dependent on the tissue and on the age of the animals.…”

“…85 However, unlike in male WKY rats, male SHR fail to upregulate renal expression of antioxidant enzymes when oxidative stress is increased with molsidomine. 85 Whether oxidative stress is higher in male or female SHR is dependent on the tissue and on the age of the animals. In kidneys, oxidative stress, measured as increases in F2-isoprostane or lucigenin chemiluminescence, is slightly lower or similar in females and males.…”

“…BP in male SHR is reduced with antioxidants, such as tempol or apocynin, but not in females. 85 Sullivan and colleagues reported that the activities of superoxide dismutase and catalase were augmented in kidneys from male SHR compared to females. 86 Renal antioxidant enzyme expression is higher in male SHR than in females.…”

“…In kidneys, oxidative stress, measured as increases in F2-isoprostane or lucigenin chemiluminescence, is slightly lower or similar in females and males. 85 However, we have not examined whether renal damage in aging male SHR is ameliorated with chronic antioxidants, although BP is reduced, and therefore renal injury is also likely lessened. Whether in humans antioxidant therapy can attenuate or prevent CKD is unclear at the present.…”