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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。
In order to explore the role of substance P (SP) in the pathogenesis of renal hypertension, this experiment observed the changes of SP content in different parts of the central nervous system of renovascular hypertensive rats (RHR) induced by one side renal artery stenosis Antihypertensive effects of D-Pro ~ 2, D-Phe ~ 7, D-Trp ~ 9-SP (D-SP) injected into spinal subarachnoid space (ith) The results showed that the contents of SP in rostral ventrolateral medullae (RVM) and lateral thoracic spinal cord (IML) in RHR were significantly higher than those in sham-operation control group, while there was no significant difference in SP content in hypothalamus between two groups. ith SP receptor blockers can reduce the arterial blood pressure of RHR to normal levels. In control animals, arterial blood pressure was reduced to spinal cord animals. Because RVM is an important cardiovascular center, axons of SP neurons that accumulate here project downward into the lateral horn of sympathetic preganglionic neurons in the spinal cord, and SP can cause excitatory sympathetic preganglionic neurons, And through the sympathetic adrenal medullary system of the cardiovascular system to produce excitatory effects. Therefore, the above experimental results suggest that in RHR may be due to the abnormal increase of SP content of RVM and IML, thereby promoting the sympathetic-adrenal medulla function more hyperthyroidism; suggesting central abnormal increase in SP content may play a role in the pathogenesis of renal hypertension. The application of reducing medulla oblongata spinal cord SP neural activity level of measures may be a new way to treat renal hypertension.