The effect of bolus administration of adenosine 5'-triphosphate (ATP) into the portal vein on hepatic arterial pressure (the transhepatic action of ATP) and portal venous pressure, and the contribution of nitric oxide towards these responses, was studied in the in vitro dual-perfused rabbit liver. 2. At basal tone, hepatic arterial and portal venous vasoconstriction followed ATP injection, while at a tone raised with methoxamine (10(-6)-10(-5) M) ATP caused hepatic arterial vasodilatation, and a phasic vasodilatation followed by vasoconstriction in the portal venous vascular bed. 3. To determine whether the transhepatic arterial dilatation was due to the diffusion of nitric oxide (NO) from the portal venous vasculature, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), an inhibitor of NO synthesis, was infused selectively into the portal vein. L-NAME infusion potentiated portal venous vasoconstriction to ATP (-log M ED50 5.32 +/- 0.31 to 6.51 +/- 0.43, P < 0.05, Student's paired t test) indicating the possible inhibition of a NO-mediated vasodilator component of the portal venous response to ATP. There was, however, no demonstrable difference in the transhepatic arterial vasodilatation induced by ATP during this infusion. 4. Simultaneous perfusion of both the hepatic arterial and portal venous inflows with L-NAME (100 microM) resulted in a significant decrease in the amplitude of hepatic arterial responses to ATP demonstrating that these responses were ultimately mediated by an NO-dependent mechanism. 5. This study has thus demonstrated a vasodilator component of the portal venous response to ATP that is NO-mediated. It also provides evidence that it is not portally-derived NO, but NO released from the hepatic arterial vascular bed, that accounts for the hepatic arterial vasodilatation to intra-portal administration of ATP. This implies that ATP itself, and not a second messenger, diffuses from the portal venous to hepatic arterial vascular bed to elicit the hepatic arterial response.
摘要
在体外双灌注兔肝脏模型中，研究了向门静脉大剂量注射5'-三磷酸腺苷（ATP）对肝动脉压（ATP的经肝作用）和门静脉压的影响，以及一氧化氮在这些反应中的作用。2. 在基础张力下，注射ATP后肝动脉和门静脉出现血管收缩，而在用甲氧明（10(-6)-10(-5) M）升高张力后，ATP引起肝动脉血管舒张，门静脉血管床则出现先阶段性血管舒张后血管收缩。3. 为了确定经肝动脉舒张是否是由于一氧化氮（NO）从门静脉系统扩散所致，将NO合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，100 microM）选择性注入门静脉。注入L-NAME增强了门静脉对ATP的血管收缩作用（-log M ED50从5.32±0.31变为6.51±0.43，P<0.05，配对t检验），表明可能抑制了门静脉对ATP反应中由NO介导的血管舒张成分。然而，在此注入过程中，ATP诱导的经肝动脉舒张没有明显差异。4. 同时向肝动脉和门静脉流入道灌注L-NAME（100 microM）导致肝动脉对ATP反应的幅度显著降低，表明这些反应最终由依赖NO的机制介导。5. 因此，本研究证明了门静脉对ATP反应中存在由NO介导的血管舒张成分。它还提供了证据，即导致肝动脉对门静脉内注射ATP出现血管舒张的不是来自门静脉的NO，而是从肝动脉血管床释放的NO。这意味着是ATP本身，而不是第二信使，从门静脉扩散到肝动脉血管床引发肝动脉反应。
