Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease The PREVENCION Study
Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease The PREVENCION Study
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DOI：
10.1161/hypertensionaha.108.120352
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发表时间：
2008-12-01
期刊：
影响因子：
8.3
通讯作者：
Medina-Lezama, Josefina
中科院分区：
文献类型：
--
作者：
Chirinos, Julio A.;David, Robert;Medina-Lezama, Josefina
内源性一氧化氮合酶抑制剂（end-NOSI）与心血管危险因素和动脉粥样硬化有关。此外，终末NOSI可能通过血流动力学效应直接导致高血压。我们的目的是研究末端 NOSI 不对称二甲基精氨酸 (ADMA) 和 N-胍基单甲基精氨酸 (NMMA)、亚临床动脉粥样硬化和动脉血流动力学之间的关联。我们对参与一项基于人群的研究（预防研究）的 922 名成年人进行了研究，并使用线性回归检查了末端 NOSI/L-精氨酸与动脉血流动力学、颈动脉-股动脉脉搏波速度和颈动脉内膜-中层厚度之间的相关性。研究发现 ADMA、NMMA 和 L-精氨酸与各种经典心血管危险因素存在差异相关。即使在调整心血管危险因素、C 反应蛋白和肾功能后，ADMA 和 NMMA（但不是 L-精氨酸）仍是颈动脉内膜中层厚度的显着预测因子。相反，ADMA 和 NMMA 不能预测颈动脉-股动脉脉搏波速度、血压或血流动力学异常。较高的 L-精氨酸独立预测收缩期高血压、较高的中心脉压、入射波振幅、中心增强压和较低的总动脉顺应性，但不能预测全身血管阻力或心输出量。我们得出结论，ADMA 和 NMMA 与心血管危险因素存在差异相关，但两种最终 NOSI 都是颈动脉粥样硬化的独立预测因子。相反，它们与大动脉僵硬、高血压或血流动力学异常无关。我们的研究结果与不对称精氨酸甲基化在动脉粥样硬化中的作用一致，但在大动脉硬化、高血压或长期血流动力学调节中则不然。 L-精氨酸与异常脉动（而非阻力）动脉血流动力学指数独立相关，这可能反映异常的 L-精氨酸转运，导致细胞内 NO 合成生物利用度降低。 （高血压。2008 年；52：1051-1059。）
Endogenous NO synthase inhibitors (end-NOSIs) have been associated with cardiovascular risk factors and atherosclerosis. In addition, end-NOSIs may directly cause hypertension through hemodynamic effects. We aimed to examine the association between end-NOSI asymmetrical dimethylarginine (ADMA) and N-guanidino-monomethylarginine (NMMA), subclinical atherosclerosis, and arterial hemodynamics. We studied 922 adults participating in a population-based study (PREVENCION Study) and examined the correlation between end-NOSI/L-arginine and arterial hemodynamics, carotid-femoral pulse wave velocity, and carotid intima-media thickness using linear regression. ADMA, NMMA, and L-arginine were found to be differentially associated with various classic cardiovascular risk factors. ADMA and NMMA (but not L-arginine) were significant predictors of carotid intima-media thickness, even after adjustment for cardiovascular risk factors, C-reactive protein, and renal function. In contrast, ADMA and NMMA did not predict carotid-femoral pulse wave velocity, blood pressure, or hemodynamic abnormalities. Higher L-arginine independently predicted systolic hypertension, higher central pulse pressure, incident wave amplitude, central augmented pressure, and lower total arterial compliance but not systemic vascular resistance or cardiac output. We conclude that ADMA and NMMA are differentially associated with cardiovascular risk factors, but both end-NOSIs are independent predictors of carotid atherosclerosis. In contrast, they are not associated with large artery stiffness, hypertension, or hemodynamic abnormalities. Our findings are consistent with a role for asymmetrical arginine methylation in atherosclerosis but not in large artery stiffening, hypertension, or long-term hemodynamic regulation. L-Arginine is independently associated with abnormal pulsatile (but not resistive) arterial hemodynamic indices, which may reflect abnormal L-arginine transport, leading to decreased intracellular bioavailability for NO synthesis. (Hypertension. 2008; 52: 1051-1059.)