Huang Hui-Chun, Wang Sun-Sang, Chan Che-Chang, Lee Fa-Yauh, Chang Full-Young, Lin Han-Chieh, Hou Ming-Chih, Tai Chun-Ching, Lai I-Nien, Lee Shou-Dong
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, No. 201, Sec 2, Shih-Pai Road, Taipei 11217, Taiwan
J Hepatol. 2004 Feb;40(2):234-8. doi: 10.1016/j.jhep.2003.10.010.
BACKGROUND/AIMS: Nitric oxide (NO), a potent vasodilator, plays a significant role in the vascular hyposensitivity to vasoconstrictors related to portal hypertension. Chronic NO inhibition ameliorates portal-systemic collaterals in portal hypertensive rats. This study investigated whether chronic NO inhibition by NG-nitro-L-arginine methyl ester (L-NAME) improves the portal-systemic collateral vascular responsiveness to arginine vasopressin (AVP) in portal hypertensive rats.
Partially portal vein-ligated (PVL) rats received L-NAME in tap water (approximately 25 mg/kg per day) or tap water only (control) since 2 days prior to until 7 days after PVL. Mean arterial pressure was measured on the 8th day. By in situ perfusion model, different concentrations of AVP (10(-10)-10(-7) M) with a constant flow rate (20 ml/min) were applied to assess the perfusion pressure of collateral vessels. In another series, perfusion with different flow rates (5-30 ml/min) was used to obtain flow-pressure curves: the slopes represent collateral vascular resistances and higher resistances indicate less collaterals.
Mean arterial pressure was higher in the L-NAME-treated group than that of the control group (P<0.05). As compared with the controls, L-NAME-treated rats achieved significantly higher perfusion pressures in response to AVP. In addition, chronic L-NAME treatment also induced an increase of collateral vascular resistance, suggesting the attenuation of portal-systemic shunting.
Chronic NO inhibition ameliorates portal-systemic shunting and improves the collateral vascular responsiveness to AVP in portal hypertensive rats.
背景/目的：一氧化氮（NO）作为一种强效血管舒张剂，在与门静脉高压相关的血管对血管收缩剂反应性降低中起重要作用。慢性抑制NO可改善门静脉高压大鼠的门体侧支循环。本研究旨在探讨通过N-硝基-L-精氨酸甲酯（L-NAME）慢性抑制NO是否能改善门静脉高压大鼠门体侧支血管对精氨酸加压素（AVP）的反应性。
部分门静脉结扎（PVL）大鼠自PVL术前2天至术后7天，饮用含L-NAME的自来水（约25mg/kg/天）或仅饮用自来水（对照组）。在第8天测量平均动脉压。通过原位灌注模型，以恒定流速（20ml/min）施加不同浓度的AVP（10-10-10-7M），以评估侧支血管的灌注压力。在另一组实验中，采用不同流速（5-30ml/min）进行灌注以获得流量-压力曲线：斜率代表侧支血管阻力，阻力越高表明侧支越少。
L-NAME治疗组的平均动脉压高于对照组（P<0.05）。与对照组相比，L-NAME治疗的大鼠对AVP的反应达到显著更高的灌注压力。此外，慢性L-NAME治疗还导致侧支血管阻力增加，提示门体分流减少。
慢性抑制NO可改善门静脉高压大鼠的门体分流，并提高侧支血管对AVP的反应性。
