Tsugawa K, Hashizume M, Migou S, Kishihara F, Kawanaka H, Tomikawa M, Tanoue K, Sugimachi K
Dept. of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Scand J Gastroenterol. 2000 Oct;35(10):1097-105. doi: 10.1080/003655200451243.
Portal hypertension is often accompanied by a hyperdynamic circulation state. Some reports have suggested that nitric oxide (NO) plays an important role in this hyperdynamic state. On the other hand, although endothelin (ET)-1, a powerful vasoconstrictor, was recently identified, little is known about its role in portal hypertension or about the interaction between NO and ET-1. The aim of this study was therefore to investigate whether or not the inhibitor of NO synthase (NOS) might improve portal hypertension, and also to clarify the relationship between NO and ET-1.
Portal hypertensive (PHT) rats, in which hypertension was induced by a two-step ligation of the portal vein (PVL), were used. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), and serum levels of NO and ET-1 were determined in PVL rats treated with two NOS inhibitors with different functions: N(G)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). Control (CTR) rats. treated by a sham operation (SO), were also studied.
Two-step PVL treatment induced a significant increase in the serum level of NO3-and ET-1 in the portal vein. L-NAME and AG administration significantly decreased PP at doses of 50 mg/kg in PHT rats after 60 min administration, while no inhibitor effected any modification in the CTBR rats. Both NOS inhibitors increased MAP and decreased PP and BFV in the portal vein, gastric mucosa, and spleen, in addition to decreasing the serum levels of NO3- and ET-1 in the PHT rats, while neither blockade modified any parameters in the CTR rats. In PHT rats, L-arginine, a NO substance, reversed the effect of L-NAME, while it did not induce any recovery from the AG effect.
In PHT rats, NO seems to contribute to portal hypertension. PVL increases not only the serum level of NO3-, but also that of ET-1 in the portal vein. Both L-NAME and AG reduce PP and BFV of the portal vein, spleen, gastric mucosa. and liver. In addition, the inhibition of NOS diminishes the serum level not only of NO, but also of ET-1. Use of an appropriate NOS inhibitor may therefore positively affect the hyperdynamic state in portal hypertension.
门静脉高压常伴有高动力循环状态。一些报告表明，一氧化氮（NO）在这种高动力状态中起重要作用。另一方面，尽管最近发现内皮素（ET）-1是一种强大的血管收缩剂，但其在门静脉高压中的作用以及NO与ET-1之间的相互作用却知之甚少。因此，本研究的目的是调查一氧化氮合酶（NOS）抑制剂是否可以改善门静脉高压，并阐明NO与ET-1之间的关系。
使用通过门静脉两步结扎（PVL）诱导高血压的门静脉高压（PHT）大鼠。在用两种具有不同功能的NOS抑制剂：N（G）-硝基-L-精氨酸甲酯（L-NAME）和氨基胍（AG）处理的PVL大鼠中，测定平均动脉压（MAP）、门静脉压力（PP）、内脏血流量（BFV）以及NO和ET-1的血清水平。还研究了通过假手术（SO）处理的对照（CTR）大鼠。
两步PVL处理导致门静脉中NO3-和ET-1的血清水平显著升高。在给药60分钟后，以50mg/kg的剂量给予L-NAME和AG可使PHT大鼠的PP显著降低，而在CTR大鼠中没有抑制剂产生任何改变。两种NOS抑制剂均可增加MAP，并降低门静脉、胃黏膜和脾脏中的PP和BFV，此外还可降低PHT大鼠中NO3-和ET-1的血清水平，而在CTR大鼠中，两种阻断均未改变任何参数。在PHT大鼠中，NO物质L-精氨酸可逆转L-NAME的作用，而它并未诱导AG作用的任何恢复。
在PHT大鼠中，NO似乎促成了门静脉高压。PVL不仅会增加门静脉中NO3-的血清水平，还会增加ET-1的血清水平。L-NAME和AG均可降低门静脉、脾脏、胃黏膜和肝脏的PP和BFV。此外，抑制NOS不仅会降低NO的血清水平，还会降低ET-1的血清水平。因此，使用适当的NOS抑制剂可能会对门静脉高压中的高动力状态产生积极影响。
