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

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。

Effect of long-term inhibition of CB1 receptor on blood pressure and vascular reactivity in spontaneously hypertensive rats

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 protein expression 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 aortic 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 Ⅱ stimulation and improve endothelium dependent or independent relaxation of aortic ring through up-regulation of eNOS expression of vascular tissue in SHR.