Therapeutic effects of angiotensin II type 1 receptor blocker at an advanced stage of hypertensive diastolic heart failure
Therapeutic effects of angiotensin II type 1 receptor blocker at an advanced stage of hypertensive diastolic heart failure
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DOI：
10.1097/hjh.0b013e328010d635
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发表时间：
2007-02-01
影响因子：
4.9
通讯作者：
Hori, Masatsugu
中科院分区：
文献类型：
--
作者：
Nishio, Mayu;Sakata, Yasushi;Hori, Masatsugu
目的血管紧张素11 1型受体阻滞剂（ARB）在收缩性心力衰竭治疗中的应用日益增多。然而，ARB在舒张性心力衰竭（DHF）治疗中的作用仍有待澄清，特别是在其晚期阶段。本实验研究的影响ARB管理的高血压DHF的先进阶段。方法达尔盐敏感的大鼠从7周的年龄喂养8%的氯化钠饮食代表明显DHF在20周的年龄，在以前的研究中指出（高血压DHF模型）。17周龄时左室舒张功能不全、心肌肥厚、纤维化、巨噬细胞浸润和活性氧生成增加，将DHF模型大鼠随机分为两组;用亚降压剂量的ARB处理6只大鼠3周（奥美沙坦0.6 mg/kg/天），结果ARB给药3周后，大鼠左室舒张末功能明显下降，左室舒张末功能明显下降，左室舒张末功能明显下降。舒张压与左心室肥厚、纤维化和舒张功能障碍的衰减相关。巨噬细胞浸润减弱，转化生长因子-P和单核细胞趋化蛋白-1的基因表达减少，在ARB治疗的大鼠左心室心肌。活性氧的产生也随着NADPH氧化酶活性的降低而减少。结论即使在晚期开始使用ARB，ARB也能在高血压DHF中发挥有益作用，与其降压作用无关。有益效果至少部分归因于通过抑制细胞因子和趋化因子产生以及NADPH氧化酶活性来减轻炎症变化和氧化应激。J Hypertens 25：455-461（c）2007 Lippincott威廉姆斯和威尔金斯。
Objective Angiotensin 11 type 1 receptor blocker (ARB) is increasingly prescribed for the treatment of systolic heart failure with a growing body of clinical evidence. The roles of ARB, however, remain to be clarified in the treatment of diastolic heart failure (DHF), particularly at its advanced stage. This experimental study investigated the effects of ARB administered at an advanced stage of hypertensive DHF.Methods Dahl salt-sensitive rats fed an 8% NaCl diet from age 7 weeks represent overt DHF at age 20 weeks, as noted in previous studies (hypertensive DHF model). The DHF model rats were randomly divided into two groups at age 17 weeks when left ventricular diastolic dysfunction, hypertrophy, fibrosis, macrophage infiltration and reactive oxygen species generation were already augmented; six rats treated for 3 weeks with a subdepressor dose of ARB (olmesartan 0.6 mg/kg per day), and six untreated rats.Results The 3-week administration of ARB significantly decreased the left ventricular end-diastolic pressure in association with attenuation of left ventricular hypertrophy, fibrosis and diastolic dysfunction. Macrophage infiltration was attenuated with decreased gene expression of transforming growth factor-P, and monocyte chemoattractant protein-1 in the left ventricular myocardium of the ARB-treated rats. The production of reactive oxygen species also decreased with NADPH oxidase activity.Conclusions ARB provides beneficial effects in hypertensive DHF independent of its anti hypertensive effects even if initiated at an advanced stage. The beneficial effects are at least partly attributed to the attenuation of inflammatory changes and oxidative stress through the suppression of cytokine and chemokine production and of NADPH oxidase activity. J Hypertens 25:455-461 (c) 2007 Lippincott Williams & Wilkins.