Hemodynamic effects of substance P and its receptor antagonist RP67580 in anesthetized rats with carbon tetrachloride-induced cirrhosis
Hemodynamic effects of substance P and its receptor antagonist RP67580 in anesthetized rats with carbon tetrachloride-induced cirrhosis
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DOI：
10.1080/00365520701685691
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发表时间：
2008-01-01
影响因子：
1.9
通讯作者：
Afdhal, Nezam H.
中科院分区：
文献类型：
--
作者：
Cardenas, Andres;Lowe, Robert;Afdhal, Nezam H.
Objective. P物质（SP）是一种血管扩张剂，可能有助于肝硬化的全身和内脏血管扩张。本研究的目的是确定SP（剂量约13 μ g/kg）及其特异性抑制剂RP 67580（剂量约300 μ g/kg）对中风大鼠和对照组的平均动脉压（MAP）和门静脉压（PP）的影响。材料和方法。在施用SP和RP 67580之前和之后测量MAP和PP。此外，一小组的哮喘大鼠预先用L-NAME阻断一氧化氮（NO）的影响，然后再测量。结果SP在两组中均产生一过性全身性低血压。SP引起癫痫大鼠PP显著增加，而对照组PP显著降低。RP 67580可降低SP的毒性作用，但不完全。RP 67580降低了哮喘组的PP，但在对照组中没有。在L-NAME预处理的哮喘大鼠中，SP给药引起MAP显著降低，但PP无显著变化。结论.外源性SP可增加动脉粥样硬化大鼠的PP，降低MAP。RP 687580降低PP和减少SP诱导的低血压大鼠。NO阻断可消除SP对PP的影响。SP参与肝硬化内脏血管扩张，这种作用可能由NO介导。
Objective. Substance P (SP) is a vasodilator that may contribute to systemic and splanchnic vasodilatation in cirrhosis. The aim of this study was to determine the effects of SP (dose -13 pg/kg) and its specific inhibitor, RP67580 (dose - 300 g/kg) on mean arterial pressure (MAP) and portal pressure (PP) in cirrhotic rats and controls. Material and methods. MAP and PP were measured before and after administering SP and RP67580. Additionally, a small group of cirrhotic rats were pretreated with L-NAME to block the effects of nitric oxide (NO) before measurements. Results. SP produced transient systemic hypotension in both groups. SP caused a significant increase in PP in cirrhotic rats and a decrease in PP in controls. RP67580 reduced the hypotensive effect of SP, but not completely. RP67580 decreased PP in the cirrhotic group but not in controls. In cirrhotic rats pretreated with L-NAME, SP administration caused a significant decrease in MAP but no significant change in PP. Conclusions. Exogenous SP increases PP and decreases MAP in cirrhotic rats. RP687580 decreases PP and reduces SP-induced hypotension in cirrhotic rats. NO blockade abolishes the effect of SP on PP. SP contributes to splanchnic vasodilatation in cirrhosis and this effect may be mediated by NO.