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年龄依赖性酒精诱导的脑动脉收缩易感性。

Age-Dependent Susceptibility to Alcohol-Induced Cerebral Artery Constriction.

作者信息

Bukiya Anna N, Seleverstov Olga, Bisen Shivantika, Dopico Alex M

机构信息

Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38103, USA.

出版信息

J Drug Alcohol Res. 2016;5. doi: 10.4303/jdar/236002. Epub 2016 Nov 27.

DOI:10.4303/jdar/236002
PMID:29391966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5790172/
Abstract

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 1 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 1 constitutes a significant contributor to age-dependent changes in the susceptibility of cerebral arteries to ethanol.

摘要

背景

年龄已被认为是导致酒精相关病理易感性的一个重要因素。

目的

我们旨在确定酒精引起的脑动脉收缩是否与年龄有关。

研究设计

我们使用大鼠大脑中动脉（MCA）体外直径监测、膜片钳技术和心肌细胞荧光标记，研究3周龄（50克）、8周龄（250克）和15周龄（440克）大鼠对酒精易感性的年龄依赖性增加。

结果

在无内皮的情况下，可观察到酒精引起的MCA收缩随年龄增加，同时大电导钙/电压门控钾通道（BK）辅助1亚基的蛋白水平和基础BK通道活性也随年龄增加。乙醇诱导的BK通道抑制随年龄增加。

结论

我们证明，与青春期前相比，在相当于青春期和成年早期的时期，MCA对乙醇诱导收缩的易感性增加。我们的研究表明，BK 1是脑动脉对乙醇易感性年龄依赖性变化的一个重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d3/5790172/08b5faf7a9db/nihms936831f7.jpg
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