中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
5期
716-720
,共5页
余孝海%李艳%丁扬%唐志强%汪金丽%范一菲%程文慧%钟明奎
餘孝海%李豔%丁颺%唐誌彊%汪金麗%範一菲%程文慧%鐘明奎
여효해%리염%정양%당지강%왕금려%범일비%정문혜%종명규
室旁核%血管紧张素II%慢性间歇性低氧%尾动脉收缩压%高血压%血管紧张素Ⅱ 1 型受体
室徬覈%血管緊張素II%慢性間歇性低氧%尾動脈收縮壓%高血壓%血管緊張素Ⅱ 1 型受體
실방핵%혈관긴장소II%만성간헐성저양%미동맥수축압%고혈압%혈관긴장소Ⅱ 1 형수체
paraventricular nucleus%angiotensin Ⅱ%chronic intermittent hypoxia%systolic blood pressure%hypertension%Ang Ⅱ type 1 receptor
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。
目的:研究下丘腦室徬覈(paraventricular nucleus, PVN)中血管緊張素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)在慢性間歇性低氧(chronic intermittent hypoxia,CIH)誘髮高血壓大鼠中的作用及機製。方法將♂SD大鼠隨機分為對照(Sham)組和慢性間歇性低氧(CIH)組(每日8 h,連續15d)。用無創套尾法測大鼠尾動脈收縮壓(SBP)和動脈插管法記錄平均動脈壓(MAP)、心率(HR),用立體定位儀進行 PVN 覈糰定位併微量註射藥物,用Western blot測定PVN中Ang Ⅱ水平及Ang Ⅱ1型受體(AT1 R)蛋白錶達。結果與Sham組相比,CIH 組大鼠PVN 內Ang Ⅱ水平及AT1 R錶達明顯增加。雙側PVN內微量註射Ang Ⅱ(0.03、0.3、3 nmol),均可劑量依賴性地升高Sham組和CIH組大鼠MAP,且CIH大鼠MAP升高更明顯;雙側PVN 內微量註射AT1 R阻斷劑氯沙坦(50 nmol),對Sham大鼠血壓沒有影響,但可使CIH大鼠血壓降低,併抑製Ang Ⅱ升壓作用。結論室徬覈中AngⅡ及AT1 R功能上調在慢性間歇性低氧誘髮大鼠高血壓中起重要作用。
목적:연구하구뇌실방핵(paraventricular nucleus, PVN)중혈관긴장소Ⅱ(angiotensin Ⅱ,Ang Ⅱ)재만성간헐성저양(chronic intermittent hypoxia,CIH)유발고혈압대서중적작용급궤제。방법장♂SD대서수궤분위대조(Sham)조화만성간헐성저양(CIH)조(매일8 h,련속15d)。용무창투미법측대서미동맥수축압(SBP)화동맥삽관법기록평균동맥압(MAP)、심솔(HR),용입체정위의진행 PVN 핵단정위병미량주사약물,용Western blot측정PVN중Ang Ⅱ수평급Ang Ⅱ1형수체(AT1 R)단백표체。결과여Sham조상비,CIH 조대서PVN 내Ang Ⅱ수평급AT1 R표체명현증가。쌍측PVN내미량주사Ang Ⅱ(0.03、0.3、3 nmol),균가제량의뢰성지승고Sham조화CIH조대서MAP,차CIH대서MAP승고경명현;쌍측PVN 내미량주사AT1 R조단제록사탄(50 nmol),대Sham대서혈압몰유영향,단가사CIH대서혈압강저,병억제Ang Ⅱ승압작용。결론실방핵중AngⅡ급AT1 R공능상조재만성간헐성저양유발대서고혈압중기중요작용。
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.