Increased cardiac endothelial nitric oxide synthase expression in patients taking angiotensin-converting enzyme inhibitor therapy
Increased cardiac endothelial nitric oxide synthase expression in patients taking angiotensin-converting enzyme inhibitor therapy
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DOI：
10.1111/j.1365-2362.2006.01715.x
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发表时间：
2006-10-01
影响因子：
5.5
通讯作者：
Darmer, D.
中科院分区：
文献类型：
--
作者：
Morawietz, H.;Rohrbach, S.;Darmer, D.
背景 血管紧张素转换酶（ACE）抑制剂的功效已在大型临床试验中得到证实，但对其潜在机制的了解仍然不完整。因此，本研究调查了 ACE 抑制剂治疗对冠状动脉疾病 (CAD) 或心力衰竭患者心脏一氧化氮 (NO) 合酶的影响。 患者和方法 通过标准校准的竞争性 RT-PCR 定量 mRNA 表达，通过蛋白质印迹定量蛋白质表达，并通过监测患有或不患有以下疾病的患者心肌组织匀浆中 NO 酶促形成过程中 [H-3] 精氨酸到 [H-3] 瓜氨酸的转化来量化 NOS 活性。择期冠状动脉搭桥术或心脏移植前接受ACE抑制剂治疗。 结果 择期冠状动脉搭桥术前接受ACE抑制剂治疗的患者心房肌中内皮NO合酶（eNOS）的mRNA表达量（amol mu g(-1) RNA）高于未接受该治疗的患者（8.9±0.7，n = 33，P）（22.5+/-4.8，n=23）。 < 0.0001)。 ACE抑制剂治疗使eNOS蛋白表达从[(9 +/- 0.7)相对单位(RUs)增加到(12 +/- 0.9) RUs，P < 0.05，分别]，心脏NOS活性从17.6 +/- 1.3增加到23.7 +/- 1.1 pmol mg(-1) min(-1)(分别P < 0.001)。 ACE 抑制不会改变诱导型和神经元 NO 合酶的表达。在心力衰竭患者的左心室中也发现了 ACE 抑制引起的 eNOS 类似的上调。内皮NOS表达和活性的增强并不是患者组之间临床特征和联合治疗差异的结果。结论eNOS表达和活性的增加可能有助于ACE抑制剂治疗CAD和心力衰竭的有益效果。
Background The efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in large clinical trials, but knowledge of the underlying mechanisms remains incomplete. Therefore, this study investigated the impact of ACE inhibitor therapy on cardiac nitric oxide (NO) synthases in patients with coronary artery disease (CAD) or heart failure.Pateints and Methods The mRNA expression was quantified by standard calibrated competitive RT-PCR, protein expression by Western blotting and NOS activity by monitoring the conversion of [H-3]arginine to [H-3]citrulline during enzymatic formation of NO in tissue homogenates of myocardium of patients with, or without, ACE inhibitor treatment before elective coronary artery bypass grafting or heart transplantation.Results The mRNA expression (amol mu g(-1) RNA) of endothelial NO synthase (eNOS) was higher (22.5 +/- 4.8, n = 23) in the atrial myocardium of patients taking ACE inhibitor treatment, before elective coronary artery bypass grafting, compared with patients not taking this therapy (8.9 +/- 0.7, n = 33, P < 0.0001). The ACE inhibitor therapy increased eNOS protein expression from [(9 +/- 0.7) relative units (RUs) to (12 +/- 0.9) RUs, P < 0.05, respectively] and cardiac NOS activity from 17.6 +/- 1.3 to 23.7 +/- 1.1 pmol mg protein(-1) min(-1) (P < 0.001, respectively). Inducible and neuronal NO synthase expression was not changed by the ACE inhibition. A similar up-regulation of eNOS by ACE inhibition was found in the left ventricles of patients with heart failure. The augmented endothelial NOS expression and activity was not the result of differences in clinical characteristics and concomitant therapy between the patient groups.Conclusion Increased eNOS expression and activity might contribute to the beneficial effects of ACE inhibitor therapy in the treatment of CAD and heart failure.