Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America.
Alcohol Research Program (ARP), Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America.
PLoS One. 2019 Mar 20;14(3):e0214336. doi: 10.1371/journal.pone.0214336. eCollection 2019.
Evidence suggests that ethanol-induced hypertension is associated with increased cardiovascular responsiveness to vasopressors in vivo and enhanced reactivity of isolated arteries to vasopressors ex vivo. The underlying mechanisms are not well understood and the contribution of ethanol metabolites to vascular effects induced by ethanol consumption are unclear. Mesenteric resistance arteries were harvested from Sprague-Dawley rats. Pressure myography was utilized to test effects of ethanol, acetaldehyde and phosphatidylethanol on myogenic tone and on vasoconstriction induced by phenylephrine, arginine vasopressin (aVP), endothelin-1 and KCl. Ethanol, acetaldehyde and phosphatidylethanol concentrations were monitored during the experiments. Ethanol concentrations in the vessel bath decreased with a half-life of 25min; acetaldehyde and phosphatidylethanol concentrations remained constant. Pretreatment with ethanol dose-dependently increased the potency of phenylephrine to induce vasoconstriction 4-fold (p<0.01). These effects were comparable when arteries were pre-treated with a single dose of ethanol for 30min and when ethanol concentrations were kept constant during 30min and 60min of pretreatment. While ethanol also dose-dependently increased the potency of aVP to induce vasoconstriction 1.7-fold (p<0.05), it did not affect vasoconstriction induced by endothelin-1 or KCl. Acetaldehyde pre-treatment (30 min) dose-dependently increased the potency of phenylephrine to induce vasoconstriction 2.7-fold (p<0.01) but did not affect other vasoconstrictor responses. Phosphatidylethanol did not affect any vasoconstrictor responses. Ethanol and its metabolites did not affect myogenic tone. These data suggest that ethanol and acetaldehyde selectively sensitize intrinsic constrictor responses upon activation of vascular α1-adrenergic and/or vasopressin receptors at clinically relevant concentrations. Our findings support the concept that enhanced vasoreactivity to vasoactive hormones contributes to the development of hypertension induced by ethanol consumption. Ex vivo exposure of resistance arteries to ethanol and acetaldehyde resembles effects of chronic ethanol consumption on intrinsic vascular function, and thus could serve as test platform to evaluate interventions aimed to mitigate vascular effects associated with ethanol consumption.
有证据表明，乙醇诱导的高血压与体内血管加压素对血管加压素的心血管反应性增加以及离体动脉对血管加压素的反应性增强有关。其潜在机制尚不清楚，并且乙醇代谢产物对乙醇消耗引起的血管作用的贡献尚不清楚。从小鼠肠系膜阻力动脉中采集。压力肌动描记术用于测试乙醇，乙醛和磷脂酰乙醇对肌原性张力以及去氧肾上腺素，精氨酸加压素（aVP），内皮素-1和 KCl 诱导的血管收缩的影响。在实验过程中监测乙醇，乙醛和磷脂酰乙醇的浓度。血管浴中的乙醇浓度半衰期为 25 分钟；乙醛和磷脂酰乙醇的浓度保持不变。乙醇预处理剂量依赖性地增加了去氧肾上腺素诱导血管收缩的效力达 4 倍（p<0.01）。当动脉用 30 分钟的单剂量乙醇预处理和当乙醇浓度在 30 分钟和 60 分钟的预处理期间保持恒定时，这些作用是可比的。虽然乙醇也剂量依赖性地增加了 aVP 诱导血管收缩的效力 1.7 倍（p<0.05），但它不影响内皮素-1或 KCl 诱导的血管收缩。乙醛预处理（30 分钟）剂量依赖性地增加了去氧肾上腺素诱导血管收缩的效力 2.7 倍（p<0.01），但不影响其他血管收缩反应。磷脂酰乙醇不影响任何血管收缩反应。乙醇和其代谢物不影响肌原性张力。这些数据表明，乙醇和乙醛在临床相关浓度下选择性地敏化血管α1-肾上腺素能和/或加压素受体激活时的固有收缩反应。我们的发现支持这样的概念，即增强对血管活性激素的血管反应性有助于由乙醇消耗引起的高血压的发展。在抵抗动脉的体外暴露于乙醇和乙醛类似于慢性乙醇消耗对内在血管功能的影响，因此可以作为测试平台来评估旨在减轻与乙醇消耗相关的血管作用的干预措施。
