Repeated ethanol exposure in female rats impairs cerebral endothelial function and increases cerebrovascular stiffness.

There are several lifestyle factors known to increase the risk for age-related cognitive decline and dementia, including chronic alcohol consumption and alcohol use disorder. Chronic alcohol use in adulthood causes decreased gray matter and atrophy in brain regions central to learning and memory, including the hippocampus. Further, people with alcohol use disorder have a high incidence of cerebral white matter hyperintensities, the hallmark of cerebral small vessel disease, suggesting a link between alcohol consumption and cerebrovascular disease. However, how ethanol exposure impacts the cerebral circulation remains unclear. Here, we investigated the effects of a single ethanol vapor exposure (12 h), repeated ethanol exposures (12 h/day for 10 days) or air exposure (controls; n = 8/group) on cerebrovascular function and structure in adult female Wistar rats, as women are more sensitive to alcohol-related brain injury. Endothelial function and myogenic reactivity of isolated and pressurized posterior cerebral arteries (PCAs), the pial artery responsible for perfusing the hippocampus, were assessed ex-vivo using pressure myography. Both single and repeated ethanol exposure impaired PCA endothelial function, however, had a differential effect on myogenic tone. Repeated ethanol exposure caused oxidative stress, vascular inflammation and reduced myogenic tone of PCAs compared to a single exposure. Further, PCAs from rats repeatedly exposed to ethanol were stiffer than arteries from controls and a single ethanol exposure, which commonly occurs with aging. These findings demonstrate that ethanol exposure rapidly impairs endothelial function in the cerebrovasculature of females and suggest that repeated exposures may result in disrupted hemodynamics and accelerated vascular aging.