Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, the Netherlands.
Neth Heart J. 2008 Sep;16(9):291-2. doi: 10.1007/BF03086167.
To explore the hypothesis that stent placement decreases dilator function of various arteries outside the stented segment and that angiotensin- (1-7) improves this function, and to assess the contribution of dilator signal compounds. A further objective was to test the hypothesis that on-stent delivery of Ang-(1-7) reduces neointima formation and improves endothelial function.
Abdominal aortic stenting or sham operation was performed in the rat four weeks after stenting and treatment with intravenous saline or Ang-(1-7) infusion (24 mug/kg/h); vasomotor function in isolated thoracic aorta and brachial and iliac artery was measured in organ baths. Furthermore, Ang-(1-7)-eluting stents were designed and placed in rat abdominal aorta. Neointima formation and aortic function were tested after four weeks.
Relaxation of the thoracic aorta to metacholine was decreased after stenting compared with shams due to a decrease in nitric oxide-mediated response (67% reduction in maximal NO-dependent response). Ang-(1-7) restored the response mainly through increased prostaglandin- and possibly also endothelial-derived hyperpolarising factor-mediated relaxation. Relaxation in the brachial artery decreased after stenting (maximal response dropped by 50%), whilst contractions to phenylephrine increased. Ang-(1-7) normalised vasomotor function. Iliac artery function remained unaltered after stenting but Ang-(1-7) increased maximal relaxations by 65%. Delivery of Ang-(1-7) by means of a drug-eluting stent improved endothelial function.
Stenting differentially affects dilator and contractile function in various arterial beds. Ang-(1-7) both improves dilator function and normalises contractile function. Delivery of protective peptides such as Ang-(1-7) from the stent is a new therapy option that merits further development and exploration. (Neth Heart J 2008;16:293-8.).
探讨支架置入术是否会降低支架段以外的各种动脉的扩张功能，以及血管紧张素-（1-7）是否可以改善这种功能，并评估扩张信号化合物的作用。进一步的目的是检验这样一个假说，即在支架上局部输送血管紧张素-（1-7）是否可以减少新生内膜的形成并改善内皮功能。
在支架置入术 4 周后，对大鼠进行腹主动脉支架置入或假手术，并给予静脉生理盐水或血管紧张素-（1-7）输注（24 微克/千克/小时）；在器官浴中测量离体胸主动脉、肱动脉和髂动脉的血管舒缩功能。此外，设计并将血管紧张素-（1-7）洗脱支架置入大鼠腹主动脉。4 周后检测新生内膜形成和主动脉功能。
与假手术相比，支架置入术后胸主动脉对甲酰胆碱的舒张反应减弱，这是由于一氧化氮介导的反应减少（最大 NO 依赖性反应减少 67%）。血管紧张素-（1-7）主要通过增加前列腺素和可能的内皮衍生超极化因子介导的舒张来恢复这种反应。支架置入术后肱动脉的舒张反应减弱（最大反应下降 50%），而对苯肾上腺素的收缩反应增加。血管紧张素-（1-7）使血管舒缩功能正常化。支架置入术后髂动脉功能保持不变，但血管紧张素-（1-7）可使最大舒张增加 65%。通过药物洗脱支架输送血管紧张素-（1-7）可改善内皮功能。
支架置入术对不同动脉床的扩张和收缩功能有不同的影响。血管紧张素-（1-7）既改善扩张功能，又使收缩功能正常化。从支架输送保护肽如血管紧张素-（1-7）是一种新的治疗选择，值得进一步开发和探索。（荷兰心脏病学杂志 2008；16：293-8.）。
