抑制一氧化氮生物合成对门脉高压鼠血流动力学的影响

研究一氧化氮(NO)在门脉高压高血流动力学中的作用。方法:用SD大鼠制备肝内型(IHPH)、肝前型门脉高压(PHPH)和门腔分流(PCS)3组模型,并以正常鼠作为对照组。每一组实验动物再分成3个亚组:NO生物合成抑制剂L-NMMA组、L-NMMA NO生物合成底物L-精氨酸组以及生理盐水安慰组。血流动力学研究用放射性微球注射技术。结果:IHPH、PHPH和PCS鼠均具有心输出量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低等高血流动力学特征。L-NMMA能逆转门脉高压鼠和门腔分流鼠的高血流动力学状态,使之恢复至正常鼠的基础水平,但并未达到正常鼠用L-NMMA后的水平。如先给予L-精氨酸,则使L-NMMA对门脉高压鼠和门腔分流鼠的心血管作用消失。结论:门静脉高压症中NO过多产生是高动力循环重要的、但并不是唯一的介质。

Effects of Inhibiting Nitric Oxide Biosynthesis on Systemic and Splanchnic Hemodynamics in Portal Hypertensive Rats

Aims: To evaluate the role of nitric oxide(NO) in hyperhemodynamics in portal hypertension; the present study investigated effects of nitric oxide synthase inhibitor L-NMMA with or without L-arginine, the substrate for the enzyme NO synthase, on the systemic and splanchnic hemodynamics in portal hypertensive rats. Methods: Ninty-seven male Sprague-Dawley rats were divided into four groups: intrahepatic portal hypertension(IHPH, n=23) by injection of CC14, prehepatic portal hypertension(PHPH, n = 26) by stenosis of the portal vein, end-to-side portacaval shunt (PCS, n=23), and sham-operated controls(SO, n=25). Animals of each group were divided into three subgroups: systemic administration of L-NMMA (50mg/kg BW, 1ml), L-NMMA(50mg/kg BW, 0.5ml) plus L-arginine(30mg/kg BW, 0.5ml) and normal saline solution(lml). The radioactive microsphere method was used for hemodynamic study. Results: There was the characteristic of hyperdynamic circulatory state including increased cardiac output and splanchnic blood flow, decreased mean arterial blood pressure, total peripheral vascular resistance and splanchnic vascular resistance in IHPH, PHPH and PCS rats. The hyperdynamic circulatory state in IHPH, PHPH and PCS rats could be effectively reversed by L-NMMA to the resting values of hemodynamics in SO rats, but not the levels after administration of L-NMMA in SO rats, indicating there is excessive production of NO in portal hypertensive and PCS rats. Administration of L-arginine counterbalanced the effects of L-NMMA on hyperdynamic circulatory state in portal hypertensive and PCS rats. Conclusions: It is concluded that NO is an important mediator of the hyperdynamic circulation in portal hypertension.