室旁核血管紧张素Ⅱ在慢性间歇性低氧诱发大鼠高血压中的作用及机制

摘要

目的：研究下丘脑室旁核（paraventricular nucleus， PVN）中血管紧张素Ⅱ（angiotensin Ⅱ，Ang Ⅱ）在慢性间歇性低氧（chronic intermittent hypoxia，CIH）诱发高血压大鼠中的作用及机制。方法将♂SD大鼠随机分为对照（Sham）组和慢性间歇性低氧（CIH）组（每日8 h，连续15d）。用无创套尾法测大鼠尾动脉收缩压（SBP）和动脉插管法记录平均动脉压（MAP）、心率（HR），用立体定位仪进行 PVN 核团定位并微量注射药物，用Western blot测定PVN中Ang Ⅱ水平及Ang Ⅱ1型受体（AT1 R）蛋白表达。结果与Sham组相比，CIH 组大鼠PVN 内Ang Ⅱ水平及AT1 R表达明显增加。双侧PVN内微量注射Ang Ⅱ（0．03、0．3、3 nmol），均可剂量依赖性地升高Sham组和CIH组大鼠MAP，且CIH大鼠MAP升高更明显；双侧PVN 内微量注射AT1 R阻断剂氯沙坦（50 nmol），对Sham大鼠血压没有影响，但可使CIH大鼠血压降低，并抑制Ang Ⅱ升压作用。结论室旁核中AngⅡ及AT1 R功能上调在慢性间歇性低氧诱发大鼠高血压中起重要作用。%Aim To determine whether AngⅡin para-ventricular nucleus (PVN)was involved in the chronic intermittent hypoxia (CIH ) induced-hypertension in rats.Methods Male Sprague-Dawley rats were ran-domly divided into Sham and CIH groups,the Sham rats were exposed to continuous normoxia,while the CIH rats were submitted to CIH (8 h per day for 15 days).The conscious noninvasive method with tail cuff was performed in rats to record the systolic blood pres-sure during establishing the model of CIH induced hy-pertension.Mean arterial pressure (MAP)and heart rate (HR)were recorded in vivo on a PowerLab data acquisition system after CIH.Rats were fixed on the stereotaxic instrument to conduct microinjection in the PVN.We used Western blot to measure Ang Ⅱ level and AngⅡtype 1 receptor (AT1 R)protein expression in PVN.Results The level of PVN Ang Ⅱin CIH rats was significantly higher than that in Sham rats,a-long with increased AT1 R protein expression.Microin-jection of Ang Ⅱ(0.03,0.3,3 nmol)in bilateral PVN dose-dependently increased MAP in both CIH and Sham rats,and this response was significantly augmen-ted in CIH rats.Losartan (50 nmol),AT1 R antago-nist,had no effect on MAP in Sham rats,but caused significant MAP decreases in CIH rats,and prevented Ang Ⅱ-induced increases in MAP in both CIH and Sham rats.Conclusion The results suggest that the increased AngⅡrelease and enhanced AT1 R activation in the PVN contribute to CIH induced-hypertension in rats.