Houghton Jan L, Philbin Edward F, Strogatz David S, Torosoff Mikhail T, Fein Steven A, Kuhner Patricia A, Smith Vivienne E, Carr Albert A
Division of Cardiology, Department of Medicine, Albany Medical College, Albany, New York 12208, USA.
J Am Coll Cardiol. 2002 Apr 17;39(8):1314-22. doi: 10.1016/s0735-1097(02)01781-3.
The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine.
Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied.
Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol.
In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans.
We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.
我们研究的目的是确定非裔美国人种族是否会调节补充L-精氨酸后冠状动脉血管内皮功能的改善情况。
内皮功能障碍是冠状动脉粥样硬化发展的早期阶段，并且与高血压和心肌病的发病机制有关。已证实，对于已确诊冠状动脉粥样硬化或有危险因素的患者，静脉输注一氧化氮前体L-精氨酸可改善内皮功能障碍。迄今为止，尚未研究L-精氨酸反应性的种族和性别模式。
对33对无冠状动脉造影显示冠状动脉疾病的非裔美国人和白人受试者进行冠状动脉和微血管反应性的侵入性检测，以响应分级冠状动脉内输注乙酰胆碱（ACh）+/-L-精氨酸。配对时考虑年龄、性别、左心室质量指数、体重指数和低密度脂蛋白胆固醇。
除了匹配参数外，冠状动脉内注射腺苷后的冠状动脉血流峰值（CBF）反应或L-精氨酸输注前对ACh的CBF峰值反应没有显著差异。然而，与输注前相比，非裔美国人作为一个群体在输注L-精氨酸后对ACh输注的CBF反应的绝对百分比改善显著更大（45±10%对4±6%，p = 0.0016），按性别划分后也是如此。这种增加的机制是通过进一步降低冠状动脉微血管阻力介导的。L-精氨酸输注还导致非裔美国人在注射ACh后心外膜扩张反应更大。
我们得出结论，与从选择性接受冠状动脉造影的队列中选取的匹配白人受试者相比，冠状动脉内输注L-精氨酸在非裔美国人中能显著增强内皮依赖性血管舒张。我们的研究结果表明，在改善微血管内皮功能障碍方面，补充L-精氨酸可能对某些目标人群具有治疗益处。鉴于非裔美国人中心肌病的患病率过高，该组微血管内皮功能障碍的药物纠正仍是一个重要的进一步研究领域，最终可能被证明具有临床意义。
