中枢5-羟色胺缺损引起的高血压及其中枢机理

HYPERTENSION INDUCED BY CENTRAL 5-HYDROXYTRYPTAMINE DEPLETION IN RATS AND ITS CENTRAL MECHANISM

目的 :建立中枢 5 羟色胺 (5 HT)缺损所致的实验性高血压大鼠 (EHR)模型并探讨其中枢机理。方法 :侧脑室埋植瘘管及药物注射。大鼠尾动脉血压及心率记录仪记录清醒大鼠动脉压 (AP)及心率 (HR)。高效液相色谱 电化学检测法 (HPLC ECD)检测大鼠脑内单胺类递质含量。结果 :①给大鼠侧脑室 (ICV)注射选择性神经化学切除剂 5 ,6 双羟色胺 (5 ,6 DHT)引起中枢 5 HT神经元缺损 ,使脑内 5 HT含量明显降低 ,平均动脉压 (mAP)升高 ,HR加快 ,并持续两周左右 ,形成EHR模型 ;②给大鼠ICV注射 5 HT及其重摄取抑制剂Fluoxetine可降低EHR的mAP ,且 5HT1A受体拮抗剂Spiperone可阻断其降压作用 ,而 5 HT2 ,5 HT3 受体拮抗剂 1 NP和ICS2 0 5 90 3对其降压作用无明显影响。结论 :①ICV注射 5 ,6 DHT使中枢 5 HT缺损可建立EHR模型 ;②该模型的形成与中枢 5 HT含量降低密切相关 ,增加中枢内、外源性 5 HT含量 ,均可使EHR的mAP明显降低 ,且其降压作用主要通过中枢 5 HT1A受体介导。

Aim:To establish the experimental hypertension rat(EHR) model induced by 5 HT depletion in the brain and to investigate its central mechanism. Methods: Fistula embedment and Intracerebroventricular injection (ICV). The mean arterial pressure (mAP) and heart rate (HR) were measured with a PS 100 programmable sphygmomanometer in conscious rats. Contents of monoamine transmitters were monitored according to the method of high performance liquid chromatography electrochemistry detection (HPLC ECD) method. Results:① ICV injection of 5, 6 DHT to conscious rats produced a marked decrease in the content of 5 HT in brain, hypertensive and tachycardiac effect and the changes of maintained for 2 weeks.②ICV injection of 5 HT and Fluoxetine (a reuptake inhibitor of 5 HT) produced a manifest dose dependent hypotensive effect in EHR. The hypotensive effect was only attenuated by selective 5 HT 1A receptor antiagonist.Conclusion:①ICV injection of 5, 6 DHT could set up experimentally hypertensive rat model.②The marked decrease in central 5 HT content may play an important role in EHR model. The mAP of EHR could be reduced by increasing endogenous and exogenous 5 HT levels in brain, while the depressor effect was mainly mediated by 5 HT 1A receptor.