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) was measured in 20 young (10F/10M; age 23±3 years [mean±SD]) and 21 older (11F/10M; age 69±9 years) 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: p=0.004). MCA CVRCO2 was not different in response to vitamin C in either group (group*condition: p=0.341). However, when separated by sex, older female participants exhibited increased MCA CVR with vitamin C (saline=0.85±0.79cm/s/mmHg; vitamin C=1.33±1.01cm/s/mmHg) compared to older male participants (saline=1.21±0.57cm/s/mmHg; vitamin C=0.99±0.47cm/s/mmHg) (sex*condition: p=0.011). : Oxidative stress selectively impairs cerebrovascular function in older adults in an artery- and sex-specific manner.