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药物治疗对急性充血性心力衰竭患者二甲基精氨酸水解酶(DDAH-1)和阳离子氨基酸转运蛋白-1(CAT-1)表达的生物学效应。

The biological effect of pharmacological treatment on dimethylaminohydrolases (DDAH-1) and cationic amino acid transporter-1 (CAT-1) expression in patients with acute congestive heart failure.

机构信息

Department of Human Movement Sciences, University G. D'Annunzio Chieti, Italy.

出版信息

Microvasc Res. 2011 Nov;82(3):391-6. doi: 10.1016/j.mvr.2011.06.003. Epub 2011 Jun 23.

DOI:10.1016/j.mvr.2011.06.003
PMID:21722652
Abstract

AIM

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) which plays an important role in controlling vascular tone and regulates the contractile properties of cardiac myocytes. The aim of this study was to investigate the effect of pharmacological treatment on symmetric dimethylarginine (SDMA), ADMA and arginine plasma concentrations in patients with acute congestive heart failure (ACHF) through the evaluation of type-1 system cationic amino acid transporter-1/type 1 dimethylarginine dimethylaminohydrolases-1 (CAT-1/DDAH-1).

METHODS AND RESULTS

25 hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction<35%) were included in the study. ADMA, SDMA, and arginine plasma concentrations were assessed before and after pharmacological treatment by high performance liquid chromatography. All patients received an adequate pharmacological treatment for ACHF. ADMA and SDMA plasma levels were significantly higher after pharmacological treatment respect to baseline values (pre-treatment) (0.75 vs 0.48; 1.31 vs 1.03; p<0.01). Arginine plasma concentration was significantly lower after therapy respect to baseline values (0.78 vs 0.99; p<0.01). This is associated more with the modulation of DDAH-1 protein than with of CAT-1 system transport.

CONCLUSIONS

In patients with ACHF, acute renal impairment function and the modulation of metabolism and extracellular transport by the DDAH-1/CAT-1 system determine high ADMA and SDMA levels after therapy for acute congestive heart failure.

摘要

目的

不对称二甲基精氨酸(ADMA)是一种内源性一氧化氮(NO)抑制剂,在控制血管张力和调节心肌细胞收缩特性方面发挥着重要作用。本研究旨在通过评估 1 型阳离子氨基酸转运体 1/1 型二甲基精氨酸二甲氨基水解酶 1(CAT-1/DDAH-1)来研究药物治疗对急性充血性心力衰竭(ACHF)患者中对称二甲基精氨酸(SDMA)、ADMA 和精氨酸血浆浓度的影响。

方法和结果

本研究纳入了 25 名患有症状性急性充血性 HF(NYHA 分级 III-IV)和左心室(LV)功能受损(射血分数<35%)的住院心内科患者。通过高效液相色谱法评估药物治疗前后 ADMA、SDMA 和精氨酸的血浆浓度。所有患者均接受了针对 ACHF 的充分药物治疗。药物治疗后 ADMA 和 SDMA 血浆水平与基线值(治疗前)相比显著升高(0.75 比 0.48;1.31 比 1.03;p<0.01)。治疗后精氨酸血浆浓度与基线值相比显著降低(0.78 比 0.99;p<0.01)。这与 DDAH-1 蛋白的调节更相关,而不是 CAT-1 系统转运的调节。

结论

在 ACHF 患者中,急性肾功能损害以及 DDAH-1/CAT-1 系统对代谢和细胞外转运的调节决定了急性充血性心力衰竭治疗后 ADMA 和 SDMA 水平升高。

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