Orrego H, Carmichael F J, Israel Y
Addiction Research Foundation Clinical Institute, Toronto, Ont., Canada.
Can J Physiol Pharmacol. 1988 Jan;66(1):1-9. doi: 10.1139/y88-001.
Acute administration of ethanol increases portal blood flow by 40-60%. This increase in blood flow compensates for the increase in O2 consumption that follows alcohol intake and may play a protective role against hypoxic hepatocellular necrosis. We have investigated the mechanism of this hemodynamic effect of ethanol in the rat using the labeled microsphere technique. We ruled out a direct role of systemic glucagon and of acetaldehyde in mediating the increase in portal flow. However, the increase in flow is maximal at a blood ethanol concentration of 3.5 mM, corresponding to that required to achieve the Vmax of alcohol dehydrogenase, and is suppressed by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Alcohol ingestion results in zonal liver hypoxia and in increases in acetate, both of which have been shown to increase the levels of adenosine, a potent vasodilator, in blood and tissues. Ethanol produces a 400% increase in arterial adenosine. Adenosine infusion leads to a dose-dependent increase in portal blood flow of up to 100%, an effect that is suppressed by administration of 8-phenyltheophylline, an antagonist of adenosine at A1 and A2 receptors. Similarly, the ethanol-induced increase in portal blood flow is fully suppressed by 8-phenyltheophylline. In conclusion, adenosine appears to play an important role in the mechanism by which ethanol increases portal blood flow.
急性给予乙醇可使门静脉血流量增加40% - 60%。血流量的增加可补偿饮酒后耗氧量的增加，并可能对缺氧性肝细胞坏死起到保护作用。我们使用标记微球技术研究了乙醇在大鼠体内这种血液动力学效应的机制。我们排除了全身性胰高血糖素和乙醛在介导门静脉血流量增加中所起的直接作用。然而，血流量的增加在血液乙醇浓度为3.5 mM时达到最大，这一浓度与达到乙醇脱氢酶Vmax所需的浓度相对应，并且被乙醇脱氢酶抑制剂4 - 甲基吡唑所抑制。摄入酒精会导致肝小叶局部缺氧以及乙酸盐增加，这两者均已被证明会使血液和组织中强效血管舒张剂腺苷的水平升高。乙醇可使动脉血中腺苷增加400%。输注腺苷会导致门静脉血流量剂量依赖性增加，最高可达100%，这一效应可被A1和A2受体的腺苷拮抗剂8 - 苯基茶碱所抑制。同样，8 - 苯基茶碱可完全抑制乙醇诱导的门静脉血流量增加。总之，腺苷似乎在乙醇增加门静脉血流量的机制中发挥重要作用。
