Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease The PREVENCION Study

被引:49
作者
Chirinos, Julio A. [3 ]
David, Robert [1 ]
Bralley, J. Alexander [1 ]
Zea-Diaz, Humberto [2 ]
Munoz-Atahualpa, Edgar [2 ]
Corrales-Medina, Fernando [2 ]
Cuba-Bustinza, Carolina [2 ]
Chirinos-Pacheco, Julio [2 ]
Medina-Lezama, Josefina [2 ]
机构
[1] Metametrix Clin Lab, Duluth, GA USA
[2] Santa Maria Catholic Univ, Sch Med, Aqp, Peru
[3] Univ Penn, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
asymmetrical dimethylarginine; hypertension; atherosclerosis; arterial stiffness; hemodynamics;
D O I
10.1161/HYPERTENSIONAHA.108.120352
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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.)
引用
收藏
页码:1051 / 1059
页数:9
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