肾性高血压大鼠中枢P物质含量的变化

The Changes of Substance P Contents in Central Nervous System of Renal Hypertensive Rats

为探讨中枢P物质(substance P,SP)在肾性高血压发病中的作用,本实验观察经一侧肾动脉狭窄手术诱发的肾性高血压大鼠(RHR)中枢不同部位SP含量的变化以及脊髓蛛网膜下腔注射(ith)SP受体阻断剂D-Pro^2,D-Phe^7,D-Trp^9-SP(D-SP)所引起的降压效应。结果发现RHR的延髓腹外侧面头端(RVM)及胸段脊髓侧角(IML)SP含量均较假手术对照组明显增高;而下丘脑SP含量在两组间未见显著差异。ith SP受体阻断剂可使RHR的动脉血压降至正常水平。而在对照组动物,则可使动脉血压降至脊髓动物水平。由于RVM是重要的心血管中枢,聚集于此处的SP能神经元细胞体发出的轴突在脊髓中下行投射到侧角的交感节前神经元,而且SP可引起交感节前神经元兴奋,并通过交感一肾上腺髓质系统使心血管系统产生兴奋效应。因此上述实验结果提示在RHR可能由于RVM和IML的SP含量异常增高,从而促使交感一肾上腺髓质功能更加亢进;提示中枢SP含量的异常增高可能在肾性高血压发病中起一定的作用。而应用降低延髓一脊髓SP能神经通路活动水平的措施可能是治疗肾性高血压病的一条新途径。

The changes of substance P-like immunoreactivity(SPLI)were determined in the central nervous system of renal hypertensive rats (produced by application of a constricting clip on the left renal artery), as compared with those of sham-operated controls. The results showed that the substance SP(SP) contents in the rostral ventrolateral medulla (RVM) and intermediolateral cell column (IML) of the thoracic spinal cord in renal hypertensive rats (RHR) were significantly higher than those in the control group. On the other hand, there was no significant difference of SP content in the hypothalamus(HP) between RHR and control groups. Intrathecal injection of SP antagonist lowered the mean blood pressure in both RHR and control groups. This data suggests that the excess SP contents in RVM and IML may be closely related to the pathogenesis of hypertension.