多巴胺D4受体对血管紧张素Ⅱ介导的血管平滑肌细胞增殖的影响

D_4 dopamine receptor suppresses AngⅡ-mediated proliferation of vascular smooth muscle cells in vitro

目的观察多巴胺D4受体对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)介导的血管平滑肌细胞(vascular smoothmuscle cells,VSMCs)增殖的影响。方法以大鼠胸主动脉平滑肌细胞株(A10细胞)、原代的Wistar-Kyoto(WKY VSMCs)和自发性高血压大鼠(SHR)胸主动脉血管平滑细胞(VSMCs)为研究对象,观察刺激D4受体对AngⅡ促增殖作用的影响以及D4受体特异性阻断剂L745870对该作用的阻断效应。细胞增殖采用MTT和细胞计数方法测定。结果 AngⅡ(10-7mol/L)可促进A10细胞增殖,最大增殖幅度为64%。D4受体激动剂PD168077本身对A10细胞无增殖影响,但D4受体特异激动剂PD168077可抑制AngⅡ(10-7mol/L)介导的血管平滑肌细胞的增殖作用,最大抑制幅度为40%;应用D4受体阻断剂L745870后该抑制作用丧失;D4受体对AngⅡ介导血管增殖的作用在SHR和WKY大鼠的VSMCs之间并无区别。结论 D4受体对AngⅡ介导的血管平滑肌细胞增殖具有抑制作用,该作用可能在一定程度上抑制了高血压病所伴发的血管平滑肌细胞增殖。

Objective To investigate the effect of D4 dopamine receptor on AngiotensinⅡ（AngⅡ）mediated proliferation of vascular smooth muscle cells（VSMCs）.MethodsA10 cells（rat aortic vascular smooth muscle cells）,primary WKY（Wistar-Kyoto）and SHR（spontaneously hypertensive rat）VSMCs were used in this study under the concentration of AngⅡ from 10^-10 to 10^-6 mol/L in presence or absence of D4 dopamine receptor agonist PD168077（10^-10 to 10^-6 mol/L）or its blocker L745870（10^-7 mol/L）.The proliferation of VSMC cells was determined by MTT assay and cell counting.ResultsAngⅡ（10^-7 mol/L）enhanced proliferation of A10 cells（maximal proliferative amplitude 64%）.D4 receptor,by itself,had no effect on cell proliferation,but blocked the AngⅡ（10^-7 mol/L）-mediated proliferation of A10 cells（maximal inhibitory effect 40%）,while the effect was inhibited in the presence of D4 receptor blocker L745870.The above-mentioned effect of D4 receptor on AngⅡ-mediated proliferation had no difference between SHR and WKY VSMCs.ConclusionActivation of D4 receptor inhibits AngⅡ-mediated proliferation of vascular smooth muscle cells,which might be helpful to alleviate the proliferation of VSMCs in essential hypertension.