THE ROLE OF PROSTAGLANDINS IN MEDIATING THE EFFECTS OF ALCOHOL ON SMOOTH MUSCLE

我们的目的是调查前列腺素 分布及其前体池受酒精剂量和 暴露的持续时间和时间有助于改变 心血管状态。血管平滑肌要么暴露在酒精中 在体外或通过使用我们的自动仪器的吸入技术 精确控制酒精蒸气和血液浓度(BAC)。一位急性病 暴露在中等酒精水平会降低收缩的幅度 与血栓烷(TXA-2)类似，而较高的水平不会影响 回应。观察到的血管收缩能力的抑制与 PGI-2/TXA-2比值显著升高。在更高的水平上 酒精起到了痉挛的作用，通过这种方式增加了细胞内的钙离子 可中和前列腺素(PG)的抑郁作用，如 前列环素(PGI-2)对血管收缩的影响。长期接触 中度BAC导致轻度高血压。此外，长期饮酒 吸入显著降低血管PG水平，并诱导轻度 对血栓性贫血的高反应性。PG水平的这种抑郁可能是 部分由于脂肪酸底物的耗尽，例如 二高马来林烯酸和花生四烯酸；含量相反 与接触时间有关，降幅高达52%。 同样，长期接触高酒精水平会降低血浆PG 并对强效升压剂产生明显的高反应性。一个 高盐饮食会加剧这两种慢性酒精影响。AS 预期非类固醇抗炎药治疗酒精-幼稚 大鼠对这些药物的血管反应性也有类似的增加。 这些数据与长期接触酒精的假设是一致的 对PG系统有阿司匹林样的影响，如改变的反映 伸缩性。这些影响仅在依赖的受试者中发生(至少3 酒精暴露天数)，并随着暴露时间的延长而增加。 初步研究结果表明，喂食大鼠双高马来宁酸 部分逆转酒精引起的血浆1系列和2系列PG变化。

The objective was to investigate the proposition that the prostaglandin profile and its precursor pool are modulated by alcohol dose and the duration of exposure and theroby contributes to changes in the cardiovascular state. Vascular smooth muscle was either exposed to alcohol in vitro or by an inhalation technique using our automated apparatus for precise control of alcohol vapor and blood concentrations (BAC). An acute exposure to moderate alcohol levels decreases the amplitude of contraction to a thromboxane (TXA-2)-mimic, whereas higher levels do not effect the response. The observed depression in vascular contractility is associated with a significant increase in the PGI-2/TXA-2 ratio. At higher levels alcohol acts as a spasmogen, increasing intracellular Ca++ and in this way may counteract the depressive effects of prostaglandins (PG), such as prostacyclin (PGI-2) on vascular contractility. Chronic exposure to moderate BAC resulted in a mild hypertension. Furthermore, chronic alcohol inhalation significantly depressed vascular PG levels and induced a mild hyperreactivity to a thromboxanemimic. This depression in PG levels may be due in part to depletion of fatty acid substrates such as dihomogammalinolenic acid and arachidonic acid; content was inversely related to the duration of exposure and decreased by as much as 52%. Similarly, long-term exposure to high alcohol levels depressed plasma PG levels and induced a marked hyperreactivity to potent pressor agents. A high salt diet exacerbates both of these chronic alcohol effects. As expected, non-steroidal anti-inflammatory drug treatment of alcohol-naive rats induced a comparable increase in vascular reactivity to these agents. These data are consistent with the hypothesis that chronic alcohol exposure has a aspirin-like effects on the PG system as reflected by altered contractility. These effects occur only in dependent subjects (at least 3 days of alcohol exposure) and increase with the duration of exposure. Preliminary findings indicate that feeding rat dihomogammalinolenic acid partially reverses the plasma 1 and 2 series PG changes induced by alcohol.