Chan Che-Chang, Chang Ching-Chih, Huang Hui-Chun, Wang Sun-Sang, Lee Fa-Yauh, Chang Full-Young, Lin Han-Chieh, Tai Chun-Ching, Lee Shou-Dong
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
J Gastroenterol Hepatol. 2005 Dec;20(12):1867-72. doi: 10.1111/j.1440-1746.2005.03969.x.
Catecholamine exerts profound vascular effects on vascular smooth muscle, and serum norepinephrine (Nepi) and sympathetic nervous activity are increased in cirrhosis. The vascular response of Nepi and acetylcholine (Ach) in portal-systemic collaterals of cirrhotic rats is unknown. The purpose of the present study was to investigate the effects of Nepi and Ach on portal-systemic collaterals of common bile duct-ligated (BDL) cirrhotic rats.
Perfusion studies were performed 6 weeks after BDL when hepatic cirrhosis was induced. Three series of experiments were performed in BDL rats: (i) the Nepi (10(-10) mol/L-10(-5) mol/L) vasoconstrictory responses with (n = 6) and without (n = 5) alpha1- (phentolamine, 5 x 10(-6) mol/L) or beta- (propranolol, 10(-5) mol/L) receptor antagonist (n = 6 and 5, respectively); (ii) the Ach (10(-8) mol/L-10(-5) mol/L) vasodilatory responses in Nepi- preconstricted portal-systemic collaterals in the absence (n = 7) or presence (n = 8) of N(pi)- L-nitro-arginine (NNA, 10(-4) mol/L); and (iii) the effect of indomethacin (10(-5) mol/L; n = 6) on Nepi responses. The collateral vascular responses were evaluated by the in situ collateral perfusion.
Norepinephrine significantly increased the perfusion pressure and was inhibited by phentolamine (P < 0.05). The constrictive responses of Nepi were not significantly modified in the presence of propranolol (P > 0.05). Acetylcholine produced >50% relaxation of the Nepi-preconstricted collateral vessels and was inhibited by NNA (P < 0.05). In addition, indomethacin significantly enhanced the constrictive response of Nepi (P < 0.05).
Norepinephrine has a vasoconstrictive effect on the portal-systemic collaterals of cirrhotic rats and this effect was mediated by alpha1-receptor. Both nitric oxide and prostaglandin are endogenous modulators in the collateral circulation of cirrhotic rats.
儿茶酚胺对血管平滑肌具有显著的血管效应，肝硬化患者血清去甲肾上腺素（Nepi）和交感神经活性增加。肝硬化大鼠门体侧支循环中Nepi和乙酰胆碱（Ach）的血管反应尚不清楚。本研究旨在探讨Nepi和Ach对胆总管结扎（BDL）肝硬化大鼠门体侧支循环的影响。
在诱导肝硬化6周后进行灌注研究。在BDL大鼠中进行了三组实验：（i）Nepi（10^(-10)mol/L - 10^(-5)mol/L）在有（n = 6）和无（n = 5）α1-（酚妥拉明，5×10^(-6)mol/L）或β-（普萘洛尔，10^(-5)mol/L）受体拮抗剂情况下的血管收缩反应（分别为n = 6和5）；（ii）Ach（10^(-8)mol/L - 10^(-5)mol/L）在无（n = 7）或有（n = 8）N(pi)-L-硝基精氨酸（NNA，10^(-4)mol/L）情况下对Nepi预收缩的门体侧支循环的血管舒张反应；（iii）吲哚美辛（10^(-5)mol/L；n = 6）对Nepi反应的影响。通过原位侧支循环灌注评估侧支血管反应。
去甲肾上腺素显著增加灌注压力，并被酚妥拉明抑制（P < 0.05）。在普萘洛尔存在的情况下，Nepi的收缩反应没有显著改变（P > 0.05）。乙酰胆碱使Nepi预收缩的侧支血管舒张>50%，并被NNA抑制（P < 0.05）。此外，吲哚美辛显著增强了Nepi的收缩反应（P < 0.05）。
去甲肾上腺素对肝硬化大鼠的门体侧支循环具有血管收缩作用，且该作用由α1受体介导。一氧化氮和前列腺素都是肝硬化大鼠侧支循环中的内源性调节剂。
