Huang Hui-Chun, Chang Ching-Chih, Wang Sun-Sang, Lee Fa-Yauh, Teng Tzu-Hua, Lee Jing-Yi, Lin Han-Chieh, Chuang Chiao-Lin, Lee Shou-Dong
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
J Vasc Res. 2012;49(2):160-8. doi: 10.1159/000332347. Epub 2012 Jan 25.
BACKGROUND/AIMS: In liver cirrhosis/portal hypertension, collaterals as varices may bleed and are influenced by vasoresponsiveness. An angiotensin blockade ameliorates portal hypertension but the influence on collaterals is unknown.
Portal hypertension and cirrhosis were induced by portal vein (PVL) and common bile duct ligation (BDL). Hemodynamics, real-time PCR of angiotensin II receptors (AT(1)R, AT(2)R) in the left adrenal vein (LAV, sham) and splenorenal shunt derived from LAV (PVL, BDL) were performed. With an in situcollateral perfusion model, angiotensin II vasoresponsiveness with different preincubations was evaluated: (1) vehicle; (2) AT(1)R blocker losartan; (3) losartan plus nonselective nitric oxide synthase (NOS) inhibitor (N(ω)-nitro-L-arginine); (4) AT(2)R blocker PD123319; (5) PD123319 plus N(ω)-nitro-L-arginine; (6) N(ω)-nitro-L-arginine, and (7) losartan plus inducible NOS inhibitor aminoguanidine.
LAV AT(1)R and AT(2)R expression decreased in PVL and BDL rats. Losartan attenuated angiotensin II-elicited vasoconstriction but PD123319 had no effect. N(ω)-nitro-L-arginine but not aminoguanidine reversed the losartan effect.
Angiotensin receptors are downregulated in the collateral vessel of portal hypertensive and cirrhotic rats. The AT(1)R blockade attenuates the angiotensin II vasoconstrictive effect, suggesting AT(1)R mediates collateral vasoconstriction and the influence of AT(2)R is negligible. The lack of aminoguanidine influence indicates that endothelial NOS participates in the losartan effect.
背景/目的：在肝硬化/门静脉高压症中，作为静脉曲张的侧支循环可能会出血，并受血管反应性影响。血管紧张素阻断可改善门静脉高压，但对侧支循环的影响尚不清楚。
通过门静脉结扎（PVL）和胆总管结扎（BDL）诱导门静脉高压和肝硬化。进行血流动力学研究，以及对左肾上腺静脉（LAV，假手术组）和源自LAV的脾肾分流（PVL组、BDL组）中的血管紧张素II受体（AT(1)R、AT(2)R）进行实时聚合酶链反应。采用原位侧支循环灌注模型，评估不同预孵育条件下血管紧张素II的血管反应性：（1）溶剂；（2）AT(1)R阻滞剂氯沙坦；（3）氯沙坦加非选择性一氧化氮合酶（NOS）抑制剂（N(ω)-硝基-L-精氨酸）；（4）AT(2)R阻滞剂PD123319；（5）PD123319加N(ω)-硝基-L-精氨酸；（6）N(ω)-硝基-L-精氨酸；（7）氯沙坦加诱导型NOS抑制剂氨基胍。
PVL组和BDL组大鼠的LAV中AT(1)R和AT(2)R表达降低。氯沙坦减弱了血管紧张素II引起的血管收缩，但PD123319没有作用。N(ω)-硝基-L-精氨酸而非氨基胍逆转了氯沙坦的作用。
门静脉高压和肝硬化大鼠的侧支血管中血管紧张素受体下调。AT(1)R阻断减弱了血管紧张素II的血管收缩作用，提示AT(1)R介导侧支血管收缩，而AT(2)R的影响可忽略不计。氨基胍缺乏影响表明内皮型NOS参与了氯沙坦的作用。
