Age-Dependent Susceptibility to Alcohol-Induced Cerebral Artery Constriction

BACKGROUND: Age has been recognized as an important contributor into susceptibility to alcohol-driven pathology. PURPOSE: We aimed at determining whether alcohol-induced constriction of cerebral arteries was age-dependent. STUDY DESIGN: We used rat middle cerebral artery (MCA) in vitro diameter monitoring, patch-clamping and fluorescence labeling of myocytes to study an age-dependent increase in the susceptibility to alcohol in 3 (50 g), 8 (250 g), and 15 (440 g) weeks-old rats. RESULTS: An age-dependent increase in alcohol-induced constriction of MCA could be observed in absence of endothelium, which is paralleled by an age-dependent increase in both protein level of the calcium-/voltage-gated potassium channel of large conductance (BK) accessory β1 subunit and basal BK channel activity. Ethanol-induced BK channel inhibition is increased with age. CONCLUSIONS: We demonstrate an increased susceptibility of MCA to ethanol-induced constriction in a period equivalent to adolescence and early adulthood when compared to pre-adolescence. Our work suggests that BK β1 constitutes a significant contributor to age-dependent changes in the susceptibility of cerebral arteries to ethanol.