Carmichael F J, Saldivia V, Varghese G A, Israel Y, Orrego H
Addiction Research Foundation Clinical Institute, Toronto, Ontario, Canada.
Am J Physiol. 1988 Oct;255(4 Pt 1):G417-23. doi: 10.1152/ajpgi.1988.255.4.G417.
The increase in portal blood flow induced by ethanol appears to be adenosine mediated. Acetate, which is released by the liver during ethanol metabolism, is known to increase adenosine levels in tissues and in blood. The effects of acetate on portal blood flow were investigated in rats using the microsphere technique. The intravenous infusion of acetate (7-250 mumol.kg-1.min-1) resulted in vasodilation of the preportal vasculature and in a dose-dependent increase in portal blood flow [control, 39.1 +/- 2.6 ml.kg-1.min-1; acetate (250 mumol.kg-1. min-1), 68.7 +/- 4.0 ml.kg-1.min-1]. This acetate-induced increase in portal blood flow was suppressed by the adenosine receptor blocker, 8-phenyltheophylline. Using the A1-adenosine receptor agonist N-6-cyclohexyl adenosine and the A2-agonist 5'-N-ethylcarboxamido adenosine, we demonstrate that the effect of adenosine on the preportal vasculature is mediated by the A2-subtype of adenosine receptors. In conclusion, these data support the hypothesis that the increase in portal blood flow after ethanol administration results from a preportal vasodilatory effect of adenosine formed from acetate metabolism in extrahepatic tissues.
乙醇诱导的门静脉血流增加似乎是由腺苷介导的。乙醇代谢过程中肝脏释放的乙酸盐,已知会增加组织和血液中的腺苷水平。使用微球技术在大鼠中研究了乙酸盐对门静脉血流的影响。静脉输注乙酸盐(7 - 250 μmol·kg⁻¹·min⁻¹)导致门静脉前血管舒张,并使门静脉血流呈剂量依赖性增加[对照组,39.1 ± 2.6 ml·kg⁻¹·min⁻¹;乙酸盐(250 μmol·kg⁻¹·min⁻¹),68.7 ± 4.0 ml·kg⁻¹·min⁻¹]。腺苷受体阻滞剂8 - 苯基茶碱可抑制乙酸盐诱导的门静脉血流增加。使用A1 - 腺苷受体激动剂N⁻6 - 环己基腺苷和A2 - 激动剂5' - N⁻乙基羧酰胺腺苷,我们证明腺苷对门静脉前血管的作用是由腺苷受体的A2亚型介导的。总之,这些数据支持以下假设:乙醇给药后门静脉血流增加是由肝外组织中乙酸盐代谢形成的腺苷的门静脉前血管舒张作用所致。