Seko Yoshinori
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Clin Sci (Lond). 2006 Mar;110(3):379-86. doi: 10.1042/CS20050299.
Ang II (Angiotensin II) has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. The effects of ARBs (Ang II receptor blockers) in the treatment of hypertension, congestive heart failure and myocardial fibrosis have been analysed extensively in human trials, as well as animal models, and the focus of interest is now directed to its pleiotropic effects, especially on inflammatory disorders. To investigate the effects of a new ARB, olmesartan, on immune-mediated myocardial injury, the protective effects of olmesartan on the development of murine acute myocarditis caused by CVB3 (coxsackievirus B3) were analysed. Olmesartan and a non-specific vasodilator hydralazine lowered systolic blood pressure of mice on day 7 after virus inoculation to a similar extent. Olmesartan significantly decreased myocardial inflammation compared with controls, whereas hydralazine significantly increased this. Olmesartan significantly decreased the expression of IFN-gamma (interferon-gamma), FasL (Fas ligand), iNOS (inducible nitric oxide synthase) and PFP (pore-forming protein) in myocardial tissue, indicating that olmesartan suppressed the activation of infiltrating killer lymphocytes. Olmesartan also decreased the expression of CVB3 genomes in myocardial tissue as well as serum levels of 8-OHdG (8-hydroxy-2'-deoxyguanosine), a biomarker of oxidative-stress-induced DNA damage. The findings suggest that olmesartan prevents myocardial damage and may improve the prognosis of patients with acute myocarditis; however, further investigations are needed before clinical use.
血管紧张素II（Ang II）已被证明在各种器官的病理生理学中起关键作用，尤其是在心血管系统中。血管紧张素II受体阻滞剂（ARBs）在治疗高血压、充血性心力衰竭和心肌纤维化方面的效果已在人体试验以及动物模型中得到广泛分析，现在人们关注的焦点转向其多效性作用，尤其是对炎症性疾病的作用。为了研究新型ARB奥美沙坦对免疫介导的心肌损伤的影响，分析了奥美沙坦对柯萨奇病毒B3（CVB3）引起的小鼠急性心肌炎发展的保护作用。奥美沙坦和非特异性血管扩张剂肼屈嗪在病毒接种后第7天将小鼠的收缩压降低到相似程度。与对照组相比，奥美沙坦显著减轻心肌炎症，而肼屈嗪则显著加重心肌炎症。奥美沙坦显著降低心肌组织中γ干扰素（IFN-γ）、Fas配体（FasL）、诱导型一氧化氮合酶（iNOS）和穿孔素（PFP）的表达，表明奥美沙坦抑制浸润性杀伤淋巴细胞的激活。奥美沙坦还降低心肌组织中CVB3基因组的表达以及血清8-羟基-2'-脱氧鸟苷（8-OHdG）水平，8-OHdG是氧化应激诱导的DNA损伤的生物标志物。这些发现表明，奥美沙坦可预防心肌损伤，并可能改善急性心肌炎患者的预后；然而，在临床应用前还需要进一步研究。
