Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats
Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats
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DOI：
10.1172/jci119156
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发表时间：
1997-01-15
影响因子：
15.9
通讯作者：
Takeshita, A
中科院分区：
文献类型：
--
作者：
Takemoto, M;Egashira, K;Takeshita, A
N-ω-硝基-L-精氨酸甲酯（L-NAME）是一种一氧化氮合成抑制剂，长期给药可导致动物冠状动脉血管重塑和心肌肥大。本研究使用大鼠模型来研究血管紧张素I转换酶（ACE）在这种变化的发病机制中的作用。我们研究了以下群体，所有这些群体都在饮用水中接受了药物治疗：未处理的对照组和给予L-NAME、L-NAME和ACE抑制剂（ACEI）、L-NAME和肼苯哒嗪的对照组。在处理的第一、第四和第八周后评价心血管结构变化和组织ACE活性。在仅用L-NAME处理的大鼠中，血管重塑在治疗的第4周和第8周是明显的，并且在治疗的第8周存在心肌肥大。血管和心肌重构的特点是组织ACE活性增加和ACE在这些组织中的免疫检测。ACEI可明显减轻这些变化，但肼苯哒嗪治疗无效。因此，局部ACE表达增加可能在该模型的心血管重构的发病机制中是重要的。
The long-term administration of N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, produces coronary vascular remodeling and myocardial hypertrophy in animals. This study used a rat model to investigate the role of angiotensin I converting enzyme (ACE) in the pathogenesis of such changes. We studied the following groups, all of which received drug treatment in their drinking water: untreated controls, and those administered L-NAME, L-NAME, and an ACE inhibitor (ACEI), and L-NAME and hydralazine, Cardiovascular structural changes and tissue ACE activities were evaluated after the first, fourth, and eighth week of treatment, In rats treated with L-NAME alone, vascular remodeling was evident at the fourth and eighth week, and myocardial hypertrophy was present at the eighth week of treatment. The vascular and myocardial remodeling were characterized by increased tissue ACE activities and immunodetectable ACE in those tissues. These changes were markedly reduced by ACEI, but not by hydralazine treatment. Increased local ACE expression may thus be important in the pathogenesis of cardiovascular remodeling in this model.