Mathie R T, Ralevic V, Moore K P, Burnstock G
Department of Surgery, Hammersmith Hospital, London, United Kingdom.
Hepatology. 1996 Jan;23(1):130-6. doi: 10.1002/hep.510230118.
The contribution of nitric oxide to mesenteric arterial vasodilator responses was investigated in the isolated perfused mesenteric arterial bed of cirrhotic rats (carbon tetrachloride/phenobarbitone; n = 6). Age-matched (n = 9) and phenobarbitone-treated rats (n = 9) served as controls. Responses to the endothelium-dependent dilators acetylcholine and adenosine 5'-triphosphate (ATP) and the smooth muscle dilator (NO donor) sodium nitroprusside were investigated after tone was raised by continuous infusion of methoxamine, before and during infusion of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 30 mumol/L) +/- L-arginine (1 mmol/L). A significant hyporesponsiveness to methoxamine infusion in cirrhotic preparations (P < .05) was not fully corrected by L-NAME. There was no difference in the percentage vasodilator response to acetylcholine in the cirrhotic group compared with controls; L-NAME significantly and reversibly inhibited the dilator response in all groups. ATP elicited dose-dependent vasodilation that, in the absence of L-NAME, did not differ between the groups. By contrast, in the presence of L-NAME, ATP (5 x 10(-8) mol) produced pronounced, reversible vasoconstriction only in cirrhotic animals (P < .02). Vasodilatation attributable to sodium nitroprusside (5 x 10(-8) mol) was significantly attenuated in cirrhotic rats. The methoxamine data support the concept of mesenteric hyposensitivity to vasoconstrictor agents in cirrhosis that may be at least partly NO mediated. Increased NO activity in smooth muscle leading to decreased guanylate cyclase availability may account for the diminished vasodilator responses to sodium nitroprusside in cirrhotic preparations. The unchanged responsiveness to vasodilatation by acetylcholine (ACh) and the vasoconstriction to ATP observed during NO blockade in cirrhotic animals indicate that mesenteric endothelial NO is unchanged or possibly diminished.
在肝硬化大鼠（四氯化碳/苯巴比妥；n = 6）的离体灌注肠系膜动脉床中研究了一氧化氮对肠系膜动脉舒张反应的作用。年龄匹配的大鼠（n = 9）和苯巴比妥处理的大鼠（n = 9）作为对照。在通过持续输注甲氧明升高张力后，在输注一氧化氮合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME；30 μmol/L）±L-精氨酸（1 mmol/L）之前和期间，研究了对内皮依赖性舒张剂乙酰胆碱和5'-三磷酸腺苷（ATP）以及平滑肌舒张剂（一氧化氮供体）硝普钠的反应。肝硬化制剂中对甲氧明输注的显著低反应性（P <.05）未被L-NAME完全纠正。与对照组相比，肝硬化组对乙酰胆碱的舒张反应百分比没有差异；L-NAME在所有组中均显著且可逆地抑制了舒张反应。ATP引起剂量依赖性血管舒张，在没有L-NAME的情况下，各组之间没有差异。相比之下，在存在L-NAME的情况下，ATP（5×10⁻⁸ mol）仅在肝硬化动物中产生明显的、可逆的血管收缩（P <.02）。肝硬化大鼠中由硝普钠（5×10⁻⁸ mol）引起的血管舒张明显减弱。甲氧明的数据支持肝硬化中肠系膜对血管收缩剂低敏感性的概念，这可能至少部分由一氧化氮介导。平滑肌中一氧化氮活性增加导致鸟苷酸环化酶可用性降低，可能解释了肝硬化制剂中对硝普钠血管舒张反应减弱的原因。肝硬化动物在一氧化氮阻断期间观察到对乙酰胆碱（ACh）血管舒张反应和对ATP血管收缩反应未改变，表明肠系膜内皮一氧化氮未改变或可能减少。
