Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, United States.
Am J Physiol Regul Integr Comp Physiol. 2023 Apr 1;324(4):R480-R496. doi: 10.1152/ajpregu.00103.2022. Epub 2023 Jan 30.
Alcohol intake leading to blood ethanol concentrations (BEC) ≥ legal intoxication modifies brain blood flow with increases in some regions and decreases in others. Brain regions receive blood from the Willis' circle branches: anterior, middle (MCA) and posterior cerebral (PCA), and basilar (BA) arteries. Rats and mice have been used to identify the targets mediating ethanol-induced effects on cerebral arteries, with conclusions being freely interchanged, albeit data were obtained in different species/arterial branches. We tested whether ethanol action on cerebral arteries differed between male rat and mouse and/or across different brain regions and identified the targets of alcohol action. In both species and all Willis' circle branches, ethanol evoked reversible and concentration-dependent constriction (ECs ≈ 37-86 mM; below lethal BEC in alcohol-naïve humans). Although showing similar constriction to depolarization, both species displayed differential responses to ethanol: in mice, MCA constriction was highly sensitive to the presence/absence of the endothelium, whereas in rat PCA was significantly more sensitive to ethanol than its mouse counterpart. In the rat, but not the mouse, BA was more ethanol sensitive than other branches. Both interspecies and regional variability were ameliorated by endothelium. Selective large conductance (BK) channel block in de-endothelialized vessels demonstrated that these channels were the effectors of alcohol-induced cerebral artery constriction across regions and species. Variabilities in alcohol actions did not fully matched KCNMB1 expression across vessels. However, immunofluorescence data from mouse arteries electroporated with -coding cDNA demonstrate that KCNMB1 proteins, which regulate smooth muscle (SM) BK channel function and vasodilation, regulate interspecies and regional variability of brain artery responses to alcohol.
饮酒导致血液乙醇浓度（BEC）≥法定醉酒会改变大脑血流，导致一些区域血流量增加，而另一些区域血流量减少。大脑区域从 Willis 环分支获得血液：前、中（MCA）和后大脑（PCA）以及基底动脉（BA）。大鼠和小鼠已被用于确定介导乙醇对脑动脉影响的靶标，尽管结论可以自由互换，但数据是在不同的物种/动脉分支中获得的。我们测试了乙醇对雄性大鼠和小鼠脑动脉的作用是否不同，以及是否在不同的大脑区域存在差异，并确定了酒精作用的靶标。在这两个物种和所有 Willis 环分支中，乙醇均可诱发可逆和浓度依赖性收缩（ECs≈37-86 mM；低于乙醇-naïve 人类的致死 BEC）。尽管与去极化引起的收缩相似，但两种物种对乙醇的反应都存在差异：在小鼠中，MCA 收缩对内皮的存在/缺失高度敏感，而在大鼠中，PCA 对乙醇的敏感性明显高于其小鼠对应物。在大鼠中，但不在小鼠中，BA 比其他分支对乙醇更敏感。种间和区域变异性都通过内皮得到改善。在去内皮化血管中选择性大电导（BK）通道阻断证明，这些通道是乙醇诱导脑动脉收缩的效应器，跨越区域和物种。乙醇作用的变异性不完全与血管中 KCNMB1 的表达相匹配。然而，来自用编码 cDNA 转染的小鼠动脉的免疫荧光数据表明，调节平滑肌（SM）BK 通道功能和血管舒张的 KCNMB1 蛋白调节脑动脉对酒精的种间和区域变异性。
