Cahill P A, Hou M C, Hendrickson R, Wang Y N, Zhang S, Redmond E M, Sitzman J V
Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
Hepatology. 1998 Aug;28(2):396-403. doi: 10.1002/hep.510280216.
Portal hypertension (PHT) is characterized by increased portal pressure caused in part by a reduction in mesenteric vascular resistance. The aim of this study was to evaluate the role of endothelin (ET) and specific ET receptors in maintaining the vasculopathy of PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham-operated. ET receptor expression was determined in the superior mesenteric artery of sham and PHT rats by in situ autoradiography, radioligand binding analysis, and reverse-transcription polymerase chain reactions (RT-PCR). The pressor response to ET-1 was determined in vitro using isolated vascular rings and in vivo by measuring mean arterial pressure, splanchnic blood flow, and portal venous pressure following treatment with ET and selective ET receptor antagonists. The pressor response to ET in vitro was significantly enhanced in PHT concomitant with increased ET-A and ET-B receptor expression. There was a significant increase in the peak pressor response to ET (10 microg/kg intravenously) in portal hypertensive rats without any significant change in plasma ET-1 levels. There was no significant difference in the peak splanchnic blood flow or portal venous pressure response following ET-A receptor blockade with JKC-301 infusion (200 microg/kg intravenously). In contrast, ET-B receptor blockade with IRL-1038 (200 microg/kg intravenously) preferentially decreased splanchnic blood flow and portal venous pressure in portal hypertensive rats. These data suggest that enhanced ET-B receptor expression in portal hypertensive vessels contributes to the maintenance of elevated portal pressure in these animals.
门静脉高压症（PHT）的特征是门静脉压力升高，部分原因是肠系膜血管阻力降低。本研究的目的是评估内皮素（ET）和特定ET受体在维持PHT血管病变中的作用。通过部分门静脉结扎在Sprague-Dawley大鼠中建立PHT模型。对照动物进行假手术。通过原位放射自显影、放射性配体结合分析和逆转录聚合酶链反应（RT-PCR）测定假手术和PHT大鼠肠系膜上动脉中的ET受体表达。使用离体血管环在体外测定对ET-1的升压反应，并在体内通过测量ET和选择性ET受体拮抗剂治疗后的平均动脉压、内脏血流量和门静脉压力来测定。PHT中体外对ET的升压反应显著增强，同时ET-A和ET-B受体表达增加。门静脉高压大鼠对ET（静脉注射10μg/kg）的升压反应峰值显著增加，而血浆ET-1水平无显著变化。静脉注射JKC-301（200μg/kg）阻断ET-A受体后，内脏血流量或门静脉压力反应峰值无显著差异。相比之下，静脉注射IRL-1038（200μg/kg）阻断ET-B受体可优先降低门静脉高压大鼠的内脏血流量和门静脉压力。这些数据表明，门静脉高压血管中ET-B受体表达增强有助于维持这些动物的门静脉压力升高。
