ACE inhibitor and angiotensin II type 1 receptor blocker differently regulate ventricular fibrosis in hypertensive diastolic heart failure
ACE inhibitor and angiotensin II type 1 receptor blocker differently regulate ventricular fibrosis in hypertensive diastolic heart failure
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DOI：
10.1097/00004872-200502000-00022
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发表时间：
2005-02-01
影响因子：
4.9
通讯作者：
Masuyama, T
中科院分区：
文献类型：
--
作者：
Yamamoto, K;Mano, T;Masuyama, T
背景：心肌硬化在高血压心脏向明显舒张性心力衰竭（DHF）的转变中起着至关重要的作用，并归因于进行性心室纤维化。先前的研究揭示了血管紧张素II 1型受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEI）对另一种心力衰竭表型（收缩性心力衰竭）中胶原合成和降解的影响，收缩性心力衰竭具有不同的病理生理学;但是，在此情况下，目的探讨血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体拮抗剂（ARB）对高血压病心室纤维化调节系统的影响DHF.设计和方法Dahl盐敏感大鼠从7周龄开始喂食含有8%NaCl的饮食（DHF模型）分为三组：6只未给药大鼠，6只接受降压剂量ARB坎地沙坦酯给药的大鼠（1 mg/kg/天），从8周龄开始，6只大鼠用ACEI，盐酸替莫普利（（0.2 mg/kg/天）。6只Dahl盐敏感大鼠作为对照组，喂食正常食物。结果ARB和ACEI对心室纤维化的抑制程度相同。ACEI可降低I型胶原mRNA的表达，但降低幅度小于ARB。胶原合成的差异可能被抵消的降解：无论是在体外和原位酶谱显示，明胶酶活性更大，在与ACEI治疗的大鼠比在与ARB治疗。结论ARB和ACEI抑制高血压DHF通过不同的机制心室纤维化。(C)2005年利平科特威廉姆斯威尔金斯。
Background Promoted myocardial stiffening has a crucial role in the transition to overt diastolic heart failure (DHF) in hypertensive hearts and is attributed to progressive ventricular fibrosis. Previous studies revealed the effects of an angiotensin II type 1 receptor blocker (ARB) and an angiotensin-converting enzyme inhibitor (ACEI) on the synthesis and degradation of collagens in the other phenotype of heart failure, systolic heart failure, which has a different pathophysiology; however, little is known about their effects in DHF.Objective To investigate effects of an ACEI and an ARB on the regulatory system of ventricular fibrosis in hypertensive DHF.Design and methods Dahl salt-sensitive rats fed a diet containing 8% NaCl from age 7 weeks (DHF model) were divided into three groups: six untreated rats, six rats treated with a subdepressor dose of an ARB, candesartan cilexetil (1 mg/kg per day), from age 8 weeks, and six rats treated with a subdepress or dose of an ACEI, temocapril hydrochloride (0.2 mg/kg per day), from age 8 weeks. Six Dahl salt-sensitive rats fed on normal chow served as controls. Data were collected when animals were aged 20 weeks.Results The administration of an ARB or an ACEI inhibited ventricular fibrosis to the same degree. The ACEI decreased the level of type I collagen mRNA, but the decrease was less than that induced by the ARB. The difference in collagen synthesis was probably cancelled out by that in degradation: both in-vitro and in-situ zymography showed that gelatinase activity was greater in the rats treated with the ACEI than in those treated with the ARB.Conclusions An ARB and an ACEI inhibited ventricular fibrosis through different mechanisms in hypertensive DHF. (C) 2005 Lippincott Williams Wilkins.