Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
J Pharmacol Sci. 2010;114(3):311-9. doi: 10.1254/jphs.09335fp.
This work investigated the expression of alpha-7 nicotinic acetylcholine receptor (α7nAChR) in the left ventricle and its putative role in cardiac angiogenesis in a pressure overload rat model induced by abdominal aorta coarctation. Blood pressure and protein levels of α7nAChR were measured at 4, 8, 12, and 16 weeks after surgery. mRNA levels of α7nAChR, cardiac vagus nerve function, cardiac hypertrophy, and microvessel density of the left ventricle were determined at the final 16-week period. The role of α7nAChR in angiogenesis was evaluated. It was found that systolic blood pressure above the coarctation site was greater at 16 weeks after coarctation and expression of α7nAChR was significantly increased at both mRNA and protein levels in the left ventricle compared with the control. Positive staining for receptors was mainly focused around vessels and among the degenerated cardiomyocytes. Cardiac vagus nerve function was significantly attenuated; microvessel density was markedly increased and was associated with cardiac hypertrophy. Activation of α7nAChR induced tube formation of cultured human umbilical vein endothelial cells (HUVECs). We conclude that expression of α7nAChR was increased at 16 weeks after coarctation, and this might be a compensatory response to decreased vagus nerve function and cardiac hypertrophy and may also play a role in cardiac angiogenesis.
本研究旨在探讨α7 型烟碱型乙酰胆碱受体（α7nAChR）在腹主动脉缩窄诱导的压力超负荷大鼠模型左心室中的表达及其在心脏血管生成中的潜在作用。术后 4、8、12 和 16 周测量血压和α7nAChR 蛋白水平。在最后 16 周，测定α7nAChR、心脏迷走神经功能、心脏肥大和左心室微血管密度的 mRNA 水平。评估α7nAChR 在血管生成中的作用。结果发现，缩窄后 16 周，缩窄部位以上的收缩压升高，左心室的α7nAChR 在 mRNA 和蛋白水平上的表达均显著增加，与对照组相比。受体的阳性染色主要集中在血管周围和变性的心肌细胞之间。心脏迷走神经功能明显减弱；微血管密度显著增加，并与心脏肥大有关。激活α7nAChR 可诱导培养的人脐静脉内皮细胞（HUVECs）形成管状结构。我们得出结论，α7nAChR 的表达在缩窄后 16 周增加，这可能是对迷走神经功能下降和心脏肥大的代偿反应，也可能在心脏血管生成中发挥作用。
