Garcia-Pagán J C, Zhang J X, Sonin N, Nakanishi K, Clemens M G
Department of Biology, University of North Carolina, Charlotte 28223, USA.
Shock. 1999 May;11(5):325-9. doi: 10.1097/00024382-199905000-00004.
Microvascular impairment observed during reperfusion following ischemia (IR) is a major determinant of the development of liver injury. Previous studies have shown that hyper-responsiveness to endothelin-1 (ET-1) contributes to microvascular dysfunction following a primarily inflammatory stress induced by endotoxin. The present study investigates whether a similar hypercontractile response to ET-1 occurs in the hepatic portal system of IR rats. Pentobarbital-anesthetized Sprague-Dawley rats underwent liver ischemia of the left and medial lobes for 60 min (IR: n = 8) or a sham operation (n = 8). Six hours after reperfusion, the liver was isolated and perfused through the portal vein. Baseline portal pressure (Pp), portal flow (Qp), and sinusoidal diameter (Ds) were measured before and 3 and 10 min after adding ET-1 (1 nM). In baseline, IR livers had a significantly greater Pp, portal resistance, and Ds than sham. ET-1 significantly increased Pp and portal resistance and significantly decreased Qp and Ds in IR and sham rats. However, these effects were significantly greater in IR. The results of the present study demonstrate that IR increases the porto-hepatic contractile response to ET-1, which may further sensitize the portal circulation to elevated ET-1 and may be a prominent contributor to the development of microvascular impairment following IR.
缺血再灌注（IR）期间观察到的微血管损伤是肝损伤发生发展的主要决定因素。先前的研究表明，对内皮素-1（ET-1）的高反应性导致内毒素诱导的主要炎症应激后微血管功能障碍。本研究调查了IR大鼠肝门系统中是否发生对ET-1的类似高收缩反应。用戊巴比妥麻醉的Sprague-Dawley大鼠左叶和中叶进行60分钟的肝脏缺血（IR组：n = 8）或假手术（n = 8）。再灌注6小时后，分离肝脏并通过门静脉进行灌注。在添加ET-1（1 nM）之前、3分钟和10分钟后测量基础门静脉压力（Pp）、门静脉血流量（Qp）和肝血窦直径（Ds）。在基础状态下，IR组肝脏的Pp、门静脉阻力和Ds显著高于假手术组。ET-1显著增加了IR组和假手术组大鼠的Pp和门静脉阻力，并显著降低了Qp和Ds。然而，这些效应在IR组中显著更大。本研究结果表明，IR增加了肝门对ET-1的收缩反应，这可能会进一步使门静脉循环对内源性ET-1升高敏感，并且可能是IR后微血管损伤发生发展的一个重要因素。
