Decreased Cerebrovascular Response to CO2 in Post-menopausal Women with COPD: Role of Oxidative Stress

Chronic obstructive pulmonary disease (COPD) is associated with cerebrovascular abnormalities and an overproduction of reactive oxygen species. We hypothesized that COPD patients have oxidant-related cerebrovascular dysfunction. The main objective was to evaluate cerebrovascular reactivity and its relationship to oxidative stress in women with COPD. We studied eight women with moderate-COPD, and ten healthy women control subjects of similar age. Transcranial Doppler ultrasound assessed cerebral blood flow velocity during hypercapnia. Plasma was assessed at rest for DNA oxidation, advanced oxidation protein products, lipid peroxidation, nitrotyrosine, antioxidant enzyme activity (glutathione peroxidase and catalase), and end-product of nitric oxide metabolism. Moderate-COPD patients showed decreased cerebrovascular sensitivity to CO2 (COPD: 1.17 ± 0.54 versus Control: 2.15 ± 0.73 cm·sec·mmHg; P < 0.01). COPD patients to have higher levels of DNA and lipid oxidation, advanced oxidation protein products, and higher glutathione peroxidase activity (P<0.05). Controlling for measures of oxidative stress (DNA and lipid oxidation, advanced oxidation protein product) eliminates statistically significant differences between the COPD and control groups are eliminated in the cerebral blood flow sensitivity to CO2. Women with moderate COPD have cerebrovascular dysfunction. Our results suggest that increased levels of systemic oxidative stress may have implications in the cerebrovascular dysfunction observed during hypercapnia in COPD. Abstract word count: 200word count: 200