Albillos A, Rossi I, Cacho G, Martínez M V, Millán I, Abreu L, Barrios C, Escartín P
Department of Gastroenterology, Clínica Puerta de Hierro, Madrid, Spain.
Am J Physiol. 1995 Mar;268(3 Pt 1):G459-64. doi: 10.1152/ajpgi.1995.268.3.G459.
Experimental evidence indicates that an increased production of nitric oxide could play a role in the peripheral vasodilation of portal hypertension. To test this hypothesis in humans, we studied basal serum NO(2-) + NO3- levels and the response of forearm resistance vessels to increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine infused into the brachial artery of 12 cirrhotic patients and 10 controls. Forearm vascular resistance (FVR) was calculated from mean arterial pressure and forearm blood flow (FBF). Cirrhotics showed higher NO(2-) + NO3- levels (P < 0.05), higher FBF (P < 0.01), and lower FVR (P < 0.01) than controls. The reduction of FVR in response to every dose of methacholine was greater in cirrhotics than in controls; this was significant (P < 0.05) at the 3 and 10 micrograms/min doses. This response to methacholine was not modified by blockade of vascular prostacyclin. The response to nitroprusside was similar in both groups. The increase in FVR in response to every dose of phenylephrine was significantly (P < 0.01) lower in cirrhotics than in controls. In cirrhotics, a significant correlation (r = -0.81, P < 0.01) was found between the FVR response to the highest doses of methacholine and phenylephrine. In conclusion, cirrhotic patients show an enhanced endothelium-mediated vasodilation, which suggests an increased synthesis of nitric oxide. This defect may mediate the peripheral vasodilation and hyporeactivity to vasopressors of these patients.
实验证据表明，一氧化氮生成增加可能在门静脉高压的外周血管舒张中起作用。为了在人体中验证这一假设，我们研究了12例肝硬化患者和10例对照者的基础血清NO(2-) + NO3-水平，以及前臂阻力血管对注入肱动脉的氯化乙酰甲胆碱、硝普钠和去氧肾上腺素浓度增加的反应。根据平均动脉压和前臂血流量（FBF）计算前臂血管阻力（FVR）。肝硬化患者的NO(2-) + NO3-水平更高（P < 0.05），FBF更高（P < 0.01），FVR更低（P < 0.01）。肝硬化患者对每剂氯化乙酰甲胆碱的FVR降低幅度大于对照组；在3和10微克/分钟剂量时差异有统计学意义（P < 0.05）。这种对氯化乙酰甲胆碱的反应不受血管前列环素阻断的影响。两组对硝普钠的反应相似。肝硬化患者对每剂去氧肾上腺素的FVR增加幅度明显低于对照组（P < 0.01）。在肝硬化患者中，对最高剂量氯化乙酰甲胆碱和去氧肾上腺素的FVR反应之间存在显著相关性（r = -0.81，P < 0.01）。总之，肝硬化患者表现出增强的内皮介导的血管舒张，这表明一氧化氮合成增加。这种缺陷可能介导了这些患者的外周血管舒张和对血管加压药的反应性降低。
