Dietary cholesterol protects against alcohol-induced cerebral artery constriction.
Dietary cholesterol protects against alcohol-induced cerebral artery constriction.
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DOI：
10.1111/acer.12373
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Fedinec A
中科院分区：
文献类型：
--
作者：
Bukiya A;Dopico AM;Leffler CW;Fedinec A
酗酒是美国过量饮酒 (EtOH) 的主要形式。间歇性（例如暴饮暴食）饮酒会导致血液酒精浓度 (BAL) 达到 18-80 mM，并导致酒精性脑动脉收缩 (AIAC)。 AIAC 是由乙醇诱导的血管平滑肌中大电导钙/电压门控钾 (BK) 通道抑制引起的。调节 BK 通道介导的 AIAC 的因素仍然很大程度上未知。雄性 Sprague-Dawley 大鼠接受高胆固醇（胆固醇的 2%）饮食 18-23 周。他们的同窝仔鼠接受等热量对照饮食。通过通过闭合颅窗监测软脑膜小动脉直径以及测量分离的加压脑动脉的直径，对 AIAC 进行了体内和体外评估。甲基-β-环糊精控制脑动脉组织中的胆固醇水平，以逆转饮食引起的胆固醇积累。通过免疫荧光染色评估脑动脉肌细胞质膜上 BK 通道表面的存在。使用选择性 BK 通道阻滞剂 paxilline 评估受压脑动脉中的 BK 通道功能。将 50 mM EtOH 注射到体内颈动脉后 5 分钟内，对照组的小动脉直径减少了 20%。高胆固醇饮食的大鼠软脑膜小动脉收缩显着减少，直径仅减少 10%。然而，两组的 BAL 保持不变。在大脑中动脉解剖和体外加压 60 mmHg 后，还观察到与对照组相比，高胆固醇饮食组的 AICAC 显着降低，这种降低在内皮去除后仍然存在。高胆固醇饮食的大鼠去内皮化脑动脉中的胆固醇水平显着升高。去除过量的胆固醇后，AIAC 恢复到在正常饮食的大鼠脑动脉中观察到的水平。新鲜分离的脑动脉肌细胞中 BK 通道形成和辅助平滑肌特异性 β1 亚基的免疫荧光染色表明，高胆固醇饮食不会下调 BK 蛋白的表面存在。然而，在高胆固醇饮食的大鼠动脉中，桩碱引起的脑动脉收缩减弱。我们的数据表明膳食胆固醇可以预防 AIAC。这种保护作用是由动脉组织中胆固醇积聚和 EtOH 靶点 - BK 通道功能减弱（但不是表面存在）引起的。
Binge drinking represents the major form of excessive alcohol (EtOH) consumption in the US. Episodic (such as binge) drinking results in blood alcohol levels (BAL) of 18–80 mM, and leads to alcohol-induced cerebral artery constriction (AICAC). AICAC was shown to arise from EtOH-induced inhibition of large-conductance, calcium/voltage-gated potassium (BK) channels in the vascular smooth muscle. Factors that modulate BK channel-mediated AICAC remain largely unknown. Male Sprague-Dawley rats were placed on high-cholesterol (2% of cholesterol) diet for 18–23 weeks. Their littermates were placed on control iso-caloric diet. AICAC was evaluated both in vivo and in vitro, by means of pial arteriole diameter monitoring through a closed cranial window and diameter measurements of isolated, pressurized cerebral arteries. Cholesterol level in the cerebral artery tissue was manipulated by methyl-β-cyclodextrin to reverse dietary-induced accumulation of cholesterol. BK channel surface presence on the plasma membrane of cerebral artery myocytes was evaluated by immunofluorescence staining. BK channel function in pressurized cerebral artery was assessed using selective BK channel blocker paxilline. Within 5 minutes of 50 mM EtOH injection into carotid artery in vivo, arteriole diameter decreased by 20% in control group. Pial arteriole constriction was significantly reduced in rats on high-cholesterol diet, resulting in only 10% reduction of diameter. BAL in both groups, however, remained the same. Significant reduction of AICAC in group on high-cholesterol diet compared to control was also observed after middle cerebral artery dissection and in vitro pressurization at 60 mmHg, this reduction remaining after endothelium removal. Cholesterol level in de-endothelialized cerebral arteries was significantly increased in rats on high-cholesterol diet. Removal of excessive cholesterol content restored AICAC to the level, observed in cerebral arteries of rats on normal diet. Immunofluorescence staining of BK channel- forming and accessory, smooth muscle-specific β1 subunit in freshly isolated cerebral artery myocyte showed that high-cholesterol diet did not down-regulate surface presence of BK protein. However, paxilline-induced cerebral artery constriction was diminished in arteries from rats on high-cholesterol diet. Our data indicate that dietary cholesterol protects against AICAC. This protection is caused by cholesterol buildup in the arterial tissue and diminished function (but not surface presence) of EtOH target – BK channel.
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影响因子：
3.6
作者：
Bukiya, Anna N.;McMillan, Jacob E.;Dopico, Alex M.
通讯作者：
Dopico, Alex M.
DOI：
10.1152/nips.01387.2002
发表时间：
2002-08-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Orio, P;Rojas, P;Latorre, R
通讯作者：
Latorre, R
影响因子：
3.5
作者：
Bukiya, Anna N.;Liu, Jianxi;Dopico, Alejandro M.
通讯作者：
Dopico, Alejandro M.
影响因子：
120.7
作者：
Reynolds, K;Lewis, LB;He, J
通讯作者：
He, J
影响因子：
3.6
作者：
Asemi, Zatollah;Tabassi, Zohreh;Esmaillzadeh, Ahmad
通讯作者：
Esmaillzadeh, Ahmad