长期抑制大麻素受体-1对自发性高血压大鼠血压及血管功能的作用  

Effect of long-term inhibition of CB_1 receptor on blood pressure and vascular reactivity in spontaneously hypertensive rats

作　　者：杨大春[1] 陈晓平[1] 王利娟[1] 曹廷兵[1] 杨华[1] 冯晓丽[1] 祝之明[1] 刘道燕[1] 

机构地区：[1]全军高血压代谢病中心重庆市高血压研究所第三军医大学大坪医院野战外科研究所高血压内分泌科,重庆400042

出　　处：《中华老年心脑血管病杂志》2008年第5期364-367,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(30670839);全军"十一五"科技攻关项目(06G070)

摘　　要：目的观察长期应用内源性大麻素受体-1(CB1)抑制剂利莫那班对自发性高血压大鼠(SHR)血压及血管功能的作用。方法16只2月龄雄性SHR随机分为对照组(8只)和利莫那班组(8只)。每月测体重,无创法测鼠尾动脉收缩压;6个月后行颈动脉插管测颈动脉血压。检测大鼠胸主动脉对血管紧张素Ⅱ(AngⅡ)、去甲肾上腺素、乙酰胆碱和硝酸甘油的反应。Westernblot法检测胸主动脉内皮型一氧化氮合酶(eNOS)的表达。结果6个月后,利莫那班组体重明显低于对照组(P<0.05);鼠尾动脉和颈动脉收缩压低于对照组(P<0.05)。利莫那班组体外胸主动脉对AngⅡ诱导的收缩反应明显低于对照组(P<0.01),对乙酰胆碱及硝酸甘油诱导的舒张反应高于对照组(P<0.05)。利莫那班组胸主动脉eNOS的表达明显高于对照组(P<0.01)。结论长期抑制CB1受体能有效降低SHR血压,改善血管对AngⅡ的收缩反应及舒张功能,其机制为促进动脉eNOS的表达。Objective To examine the effects of long-term use of rimonabant,a cannabinoid-1 （CB1） receptor blocker, on blood pressure and vascular reactivity in spontaneously hypertensive rats （SHR）. Methods SHR,aged 2 months,were fed with and without rimonabant. Rimonabant was dissolved in 1 ml of drinking water at a dosage of 10 mg/kg per day by stomach intubation using a round-ended needle for 6 months. Tail-cuff systolic blood pressure （SBP） was examined. At the end of the treatment period, carotid artery blood pressure and the aortic relaxation and contraction were examined using organ bath connecting with a polygraph, eNOS proteinexpression was measured by Western blot. Results Long-term administration of rimonabant significantly reduced body weight （ P〈0. 05）. Tail SBP and SBP of carotid artery were lower in SHR fed with rimonabant than in control SHR（not fed with rimonabant）（ P〈0.05）. Ang Ⅱ-induced contraction of aclrtic ring was greater in control SHR than in SHR fed with rimonbant （ P 〈0.01）. Endothelium dependent or independent relaxation of aortic ring was greater in SHR fed with rimonabant compared with control SHR（ P 〈0.05）. Administration of rimonabant significantly increased eNOS protein expression of aortic ring. Conclusions Long-term inhibition of CB1 receptor can significantly reduce blood pressure and contraction of aortic ring to Ang Ⅱstimulation and improve endothelium dependent or independent relaxation of aortic ring through up-regulation of eNOS expression of vascular tissue in SHR.

关 键 词：大鼠 近交SHR 血压 内源性大麻酚类 血管紧张素Ⅱ 

分 类 号：R544.1[医药卫生—心血管疾病]