Yamashita Takeshi, Sekiguchi Akiko, Kato Takeshi, Tsuneda Takayuki, Iwasaki Yu-ki, Sagara Kouichi, Iinuma Hiroyuki, Sawada Hitoshi, Aizawa Tadanori
The Cardiovascular Institute, Roppongi 7-3-10, Tokyo 106-0032, Japan.
J Renin Angiotensin Aldosterone Syst. 2007 Sep;8(3):127-32. doi: 10.3317/jraas.2007.021.
Atrial fibrillation (AF) per se causes atrial endocardial dysfunction leading to local coagulation imbalance on the internal surface of the atrium, which contributes to thrombus formation in the fibrillating left atrium.
To test a hypothesis that blockade of angiotensin II type 1 receptor (AT1-receptor) prevents the endocardial dysfunction by AF, we examined the effects of olmesartan on the expression of tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) in the endocardium of the rapidly paced rat atria.
Rapid pacing induced a significant decrease in TFPI, TM and eNOS and an increase in PAI-1 protein in the left atrium. Pre-administration of low-dose olmesartan significantly prevented the down-regulation of TFPI, TM and eNOS and also attenuated the up-regulation of PAI-1. Immunohistochemistry identified these changes predominantly in the atrial endocardium. While the drug was without any effect on mRNA levels of TFPI, TM and eNOS, there was a significant decrease in its PAI-1 mRNA expression.
AT1-receptor blocker could partially prevent the atrial endocardial dysfunction by rapid atrial pacing, which would provide one theoretical basis for beneficial effects for stroke prevention in AF.
心房颤动（AF）本身会导致心房内膜功能障碍，从而引起心房内表面局部凝血失衡，这有助于在颤动的左心房中形成血栓。
为了验证血管紧张素II 1型受体（AT1受体）阻断可预防AF引起的内膜功能障碍这一假设，我们研究了奥美沙坦对快速起搏大鼠心房内膜中组织因子途径抑制剂（TFPI）、血栓调节蛋白（TM）、内皮型一氧化氮合酶（eNOS）和纤溶酶原激活物抑制剂-1（PAI-1）表达的影响。
快速起搏导致左心房中TFPI、TM和eNOS显著降低，PAI-1蛋白增加。预先给予低剂量奥美沙坦可显著预防TFPI、TM和eNOS的下调，并减弱PAI-1的上调。免疫组织化学显示这些变化主要发生在心房内膜。虽然该药物对TFPI、TM和eNOS的mRNA水平没有任何影响，但其PAI-1 mRNA表达显著降低。
AT1受体阻滞剂可部分预防快速心房起搏引起的心房内膜功能障碍，这将为AF预防中风的有益作用提供一个理论基础。
