酒精和血管内皮功能:双相效应强调了剂量的重要性
Naresh K Rajendran1, Weimin Liu1, Paul A Cahill2
1Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Alcohol, clinical & experimental research
|June 27, 2023
概括
适度饮酒对动脉内皮细胞有好处,而大量饮酒和乙甲会导致功能障碍. 乙醇对内皮的这种双相作用可能解释了酒精-动脉样硬化研究中的J形曲线.
科学领域:
- 心血管科学 心血管科学
- 内皮细胞生物学 内皮细胞生物学
- 酒精研究 酒精研究
背景情况:
- 酒精消费对动脉疾病表现出双相影响,根据摄入水平,具有保护性或有害的结果.
- 酒精对动脉健康的影响背后的机制在很大程度上是未知的.
- 内皮细胞对于保持动脉完整性至关重要,但它们对不同酒精度的反应尚未完全理解.
研究的目的:
- 研究中度和高度乙醇对人类冠状动脉内皮细胞 (HCAEC) 功能的影响.
- 为了比较乙醇及其代谢物乙甲对内皮细胞行为的影响.
- 阐明酒精对内皮细胞影响背后的机制.
主要方法:
- HCAEC暴露于模仿中度 (25 mM) 和重量 (50 mM) 消费的乙醇度.
- 通过测量屏障完整性 (TEER),炎症标记物,细胞粘附和信号通路来评估内皮功能.
- 还评估了乙甲 (10和25微米) 的作用.
主要成果:
- 适度的乙醇 (25毫米) 增强了HCAEC屏障完整性,减少了炎症反应,并促进了恒温的Notch信号.
- 高乙醇 (50毫米) 损害了屏障功能,增加了炎症和单细胞粘附,并且对Notch信号没有影响.
- 这两种乙醇度都增加了活性氧物种 (ROS) 和内皮氧化合成酶 (eNOS) 活性,度更高时效果更大. 乙甲模仿了高水平的乙醇效应.
结论:
- 乙醇对内皮细胞产生双相作用;中度水平保持非激活状态,而高水平诱导功能障碍.
- 乙甲有助于酒精诱导的内皮功能障碍.
- 剂量对于确定乙醇对动脉内皮的影响至关重要,这可能解释了有关酒精和动脉样硬化的流行病学发现.
相关概念视频
CNS Depressants: Alcohol and Nicotine
284
Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
284
Time Course of Drug Effect
2.1K
The progression of a drug's impact can be analyzed by examining both the concentration-time course and the effect-time course. The concentration-time course is determined by the drug's half-life and is influenced by factors such as its pharmacokinetics, including absorption, distribution, metabolism, and elimination. The effect of the drug is often related to its concentration in the plasma and is calculated using the maximum drug effect and the plasma concentration that generates 50...
2.1K
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
93
Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
93
Dose-Response Relationship: Overview
3.2K
Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
3.2K
Dose-Response Relationship: Potency and Efficacy
4.6K
The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it...
4.6K
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
211
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
211


