INSERM ERI-22, Agressions Vasculaires et Réponses Tissulaires, Université de Claude Bernard, Lyon I, France.
J Renin Angiotensin Aldosterone Syst. 2012 Mar;13(1):19-28. doi: 10.1177/1470320311414752. Epub 2011 Jul 5.
The interactions between the effects of the sympathetic nervous system (SNS) and angiotensin II (ANG II) on vascular extracellular matrix (ECM) synthesis were determined in rats. The mRNA and protein content of collagen I, collagen III and elastin in the abdominal aorta (AA) and femoral artery (FA) was investigated in Wistar-Kyoto rats treated for 5 weeks with guanethidine, a sympathoplegic, losartan, an ANG II AT1 receptor (AT1R) blocker, or both. The effects of noradrenaline (NE) and ANG II on collagen III and elastin mRNA, and the receptor involved, were tested in cultured vascular smooth muscle cells (VSMCs) in vitro. Guanethidine increased collagen types I and III and decreased elastin, while losartan had an opposite effect, although without effect on collagen III. The combination of treatments abrogated changes induced by simple treatment with collagen I and elastin, but increased collagen III mRNA in AA and not in FA. NE stimulated collagen III mRNA via β receptors and elastin via α1 and α2 receptors. ANG II stimulated collagen III but inhibited elastin mRNA via AT1R. Overall, SNS and ANG II exert opposite and antagonistic effects on major components of ECM in the vascular wall. This may be of relevance for the choice of a therapeutic strategy in vascular diseases.
交感神经系统（SNS）和血管紧张素 II（ANG II）对血管细胞外基质（ECM）合成的影响相互作用在大鼠中得到了确定。在使用胍乙啶（一种交感神经阻断剂）、氯沙坦（一种 ANG II AT1 受体（AT1R）阻断剂）或两者联合治疗 5 周的 Wistar-Kyoto 大鼠中，研究了腹主动脉（AA）和股动脉（FA）中胶原 I、胶原 III 和弹性蛋白的 mRNA 和蛋白含量。在体外培养的血管平滑肌细胞（VSMCs）中测试了去甲肾上腺素（NE）和 ANG II 对胶原 III 和弹性蛋白 mRNA 的影响，以及涉及的受体。胍乙啶增加了胶原 I 和胶原 III 的含量，降低了弹性蛋白的含量，而氯沙坦则产生了相反的作用，尽管对胶原 III 没有影响。联合治疗消除了单纯用胍乙啶和氯沙坦治疗引起的变化，但增加了 AA 中的胶原 III mRNA，而不是 FA 中的。NE 通过β受体刺激胶原 III mRNA，通过α1 和α2 受体刺激弹性蛋白 mRNA。ANG II 通过 AT1R 刺激胶原 III，但抑制弹性蛋白 mRNA。总的来说，SNS 和 ANG II 对血管壁 ECM 的主要成分发挥相反和拮抗的作用。这可能与血管疾病的治疗策略选择有关。
