辣椒素抑制血管紧张素Ⅱ介导的血管收缩

Capsaicin Inhibits Angiotensin Ⅱ Induced Vasoconstriction in Mice

目的观察长期应用辣椒素作为瞬时受体电位通道香草醛类受体1型(TRPV1)激动剂对C57BL/6J小鼠胸主动脉收缩功能的作用。方法2月龄的雄性C57BL/6J小鼠,完全随机分为:普通饲料组(普食组,n=12)和普通饲料+辣椒素组(辣椒素组,n=12)。干预开始及结束时测鼠尾动脉收缩压;喂养6月后,颈动脉插管测颈动脉血压及心率。取小鼠胸主动脉,利用体外血管环张力测定技术,检测其对氯化钾(KCl)、血管紧张素Ⅱ(AngⅡ)、苯肾上腺素(PE)的收缩反应。采血测血浆肾素、AngⅡ、醛固酮浓度。培养C57BL/6J小鼠胸主动脉血管平滑肌细胞(VSMC),辣椒素(1μmol/L)孵育24 h后,应用Western-blot法检测VSMC的AngⅡ1型受体(AT1R)的表达,应用比率荧光成像系统测定AngⅡ(1μmol)对细胞内游离钙浓度的影响。结果6月后,两组间鼠尾动脉收缩压和颈动脉平均动脉压及心率无显著性差异。两组间胸主动脉对PE诱导的收缩反应无显著性差异;辣椒素组胸主动脉对AngⅡ诱导的收缩反应[(37.5±1.6)%]明显低于普食组[(59.8±1.4)%,P<0.05]。两组间血浆肾素、AngⅡ、醛固酮浓度无显著差异。培养的VSMC,辣椒素干预后AT1R蛋白表达仅为普食组的(62.4±16.6)%(P<0.05)。辣椒素组AngⅡ诱导的细胞内游离钙浓度(0.91±0.12)增加低于对照组(1.37±0.35,P<0.05)。结论应用辣椒素激活TRPV1受体能有效抑制动脉血管对AngⅡ的收缩反应,其机制与下调AT1R的表达,降低AngⅡ诱导的细胞内游离钙增加有关。

Objective To study the long-term effect of administration（6 months） with transient receptor potential vanilloid 1 （TRPV1） agonist capsaicin on contractile reactivity of thoracic aorta in C57BL/6J mice. Methods Tow-month-old male C57BL/6J mice were received normal diet group （n= 12） or capsaicin group （normal diet plus capsaicin, n= 12）. Tail-cuff systolic blood pressure （SBP） was examined at the baseline and at the end of the intervention. After 6-month treatment period, carotid artery blood pressure and heart rate were determined by catheterization, and the aortic contractile response was examined using isometric myograph （Danish Myotech Technology, Denmark）. Plasma levels of renin, angiotensin Ⅱ （Ang Ⅱ ） and aldosterone were determined. Vascular smooth muscle cells （VSMC） were obtained from thoracic aorta of mice and cultured. Angiotensin Ⅱ type 1 receptor （AT1R） protein expression was detected by western blot. Calcium imaging was detected in cultured VSMC using the fluorescent dye technique. Results Systolic blood pressure, invasive carotid artery blood pressure and heart rate have no difference between two groups. No differences was found in PE-induced contraction response in thoracic aorta; while Ang Ⅱ induced contractility of aortic ring was lower in mice with capsaicin than control group [capsaicin： （37.5 ± 1.6） % vs （59.8± 1.4） % ,P〈0.05]. Capsaicin significantly reduced AT1 R protein expression to only （62.4 ± 16.6 ） % level of control and decreased Ang Ⅱ-induced calcium entry in cultured VSMC [capsaicin： （0.91±0. 12） vs （1.37±0.35）, P〈0.05] with no differences in plasma renin Ang Ⅱ and aldosterone between the two groups. Conclusion Long-term dietary capsaicin significantly bluntes Ang Ⅱ induced contraction response in aortic segments, which may attribute to the down-regulation of AT1R expression and reduction of Ang Ⅱ-induced calcium entry in VSMC.