Oxidative stress suppresses internal carotid artery dilation to hypercapnia in healthy older adults.

Cerebrovascular disease and dementia risk increases with age, and lifetime risk is greater in women. Cerebrovascular dysfunction likely precedes cerebrovascular disease and dementia but the mechanisms are incompletely understood. We hypothesized that oxidative stress mediates cerebrovascular dysfunction with human aging. Internal carotid artery dilation (ICA dilation) and middle cerebral artery cerebrovascular reactivity (MCA CVR) in response to hypercapnia (5% CO) were measured in 20 young [10 F/10 M; age 23 ± 3 yr (means ± SD)] and 21 older (11 F/10 M; age 69 ± 9 yr) adults during intravenous infusions of saline (control) and vitamin C (acutely reduced oxidative stress condition). ICA dilation increased in response to vitamin C infusion in older adults (saline = 4.3 ± 2.4%; vitamin C = 6.7 ± 3.3%) but was unchanged in young adults (saline = 6.1 ± 2.7%; vitamin C = 5.5 ± 1.9%) (group × condition: = 0.004). MCA CVR was not different in response to vitamin C in either group (group × condition: = 0.341). However, when separated by sex, older female participants exhibited increased MCA CVR with vitamin C (saline = 0.85 ± 0.79 cm/s/mmHg; vitamin C = 1.33 ± 1.01 cm/s/mmHg) compared with older male participants (saline = 1.21 ± 0.57 cm/s/mmHg; vitamin C = 0.99 ± 0.47 cm/s/mmHg) (sex × condition: = 0.011). Oxidative stress selectively impairs cerebrovascular function in older adults in an artery- and sex-specific manner. This study is the first to report oxidative stress-mediated suppression of cerebrovascular reactivity to hypercapnia in the internal carotid artery in older compared with young adults. Overall, these in vivo findings identify oxidative stress as an important pathophysiological contributor to cerebrovascular aging in humans, highlighting the need to identify novel interventions that can reduce oxidative stress in the aging population.