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急性和慢性乙醇暴露对大鼠主动脉对血栓素类似物U46619反应的影响。

Effects of acute and chronic ethanol exposure on the response of rat aorta to a thromboxane mimic, U46619.

作者信息

Karanian J W, Salem N

出版信息

Alcohol Clin Exp Res. 1986 Mar-Apr;10(2):171-6. doi: 10.1111/j.1530-0277.1986.tb05067.x.

DOI:10.1111/j.1530-0277.1986.tb05067.x
PMID:3521375
Abstract

The spasmogenic properties of a stable thromboxane mimic, U46619, were determined in the isolated rat aorta after 1, 4, 8, or 12 hr of acute ethanol exposure in vitro or after 12 days of chronic exposure by inhalation. Acute ethanol exposure (87-822 mM) increased the baseline tension of aortic rings in a concentration-dependent manner. Moderate concentrations of ethanol (11 and 43 mM) decreased the maximum tensile response of rat aortic rings to U46619 after 8 and 4 hr of exposure, respectively. In contrast, higher ethanol concentrations (87 and 411 mM) did not significantly effect the maximum tensile response to U46619. Ethanol at 822 mM completely inhibited the response to U46619 and this inhibition could be 85% reversed after removal of ethanol. The inhibitory effect of 1.64 M ethanol was irreversible. Sensitivity to U46619 was inversely related to the ethanol concentration (greater than or equal to 43 mM) and incubation time. Similarly, chronic exposure to moderate blood ethanol levels (92-198 mg/100 ml) for 12 days decreased the maximum tensile response whereas high levels did not effect aortic contractility in vitro. Sensitivity of aorta from rats with mean blood ethanol levels greater than or equal to 92 mg/100 ml decreased at least one order of magnitude. The results suggest that the effect of physiologically tolerable ethanol concentrations on the amplitude of the tensile response to U46619 is biphasic both during acute exposure in vitro or following a chronic exposure period in vivo and the inhibitory effect on sensitivity for U46619 is both concentration- and time-dependent in the rat aorta preparation.

摘要

在体外急性乙醇暴露1、4、8或12小时后,或经吸入慢性暴露12天后,在离体大鼠主动脉中测定了稳定血栓素类似物U46619的致痉挛特性。急性乙醇暴露(87 - 822 mM)以浓度依赖的方式增加了主动脉环的基线张力。中等浓度的乙醇(11和43 mM)分别在暴露8小时和4小时后降低了大鼠主动脉环对U46619的最大张力反应。相比之下,较高浓度的乙醇(87和411 mM)对U46619的最大张力反应没有显著影响。822 mM的乙醇完全抑制了对U46619的反应,去除乙醇后这种抑制作用可逆转85%。1.64 M乙醇的抑制作用是不可逆的。对U46619的敏感性与乙醇浓度(大于或等于43 mM)和孵育时间呈负相关。同样,慢性暴露于中等血液乙醇水平(92 - 198 mg/100 ml)12天会降低最大张力反应,而高乙醇水平在体外对主动脉收缩性没有影响。平均血液乙醇水平大于或等于92 mg/100 ml的大鼠主动脉的敏感性至少降低了一个数量级。结果表明,在体外急性暴露期间或体内慢性暴露后,生理上可耐受的乙醇浓度对U46619张力反应幅度的影响是双相的,并且在大鼠主动脉制备中,对U46619敏感性的抑制作用是浓度和时间依赖性的。

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