Panza J A, Casino P R, Badar D M, Quyyumi A A
Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Circulation. 1993 May;87(5):1475-81. doi: 10.1161/01.cir.87.5.1475.
Patients with essential hypertension have a deficit in the endothelium-derived nitric oxide system that results in impaired endothelium-dependent vascular relaxation. The objective of this study was to determine whether this abnormality is caused by a deficiency of substrate for nitric oxide synthesis.
The vascular responses to acetylcholine (an endothelium-dependent vasodilator infused at 7.5, 15, and 30 micrograms/min) and sodium nitroprusside (a direct smooth muscle dilator infused at 0.8, 1.6, and 3.2 micrograms/min) were studied during combined administration of dextrose 5% or L-arginine (substrate for nitric oxide synthesis infused at 40 mumol/min) in 12 normal control subjects (seven men and five women; age, 49.3 +/- 7 years) and 14 hypertensive patients (nine men and five women; age, 48.4 +/- 7 years). In addition, the effect of D-arginine (stereoisomer of arginine that is not a precursor of nitric oxide) on the vascular responses to acetylcholine was studied in eight normal control subjects and seven hypertensive patients. Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain gauge plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with normal control subjects (maximum flow, 8.9 +/- 5 versus 15.7 +/- 6 mL.min-1.100 mL-1, respectively; p < 0.007); however, no difference was observed in the response to sodium nitroprusside (11.4 +/- 6 and 11.7 +/- mL.min-1.100 mL-1, respectively). L-Arginine did not significantly change basal blood flow or vascular resistance in either group. In normal control subjects, the infusion of L-arginine significantly augmented the vasodilator response to acetylcholine (maximum flow, 15.7 +/- 6 versus 21.4 +/- 8 mL.min-1.100 mL-1 before and after L-arginine, respectively; p < 0.001). In contrast, in hypertensive patients, the infusion of L-arginine did not alter the response to acetylcholine (maximum flow, 8.9 +/- 5 and 8.4 +/- 4 mL.min-1.100 mL-1 before and after L-arginine, respectively). The administration of L-arginine did not modify the response to sodium nitroprusside in either group. Similarly, the infusion of D-arginine did not alter the response to acetylcholine in either group.
In normal humans, availability of substrate for production of nitric oxide is a rate-limiting step for endothelium-dependent vascular relaxation. In contrast, increased availability of nitric oxide precursor does not modify endothelium-mediated vasodilation in hypertensive patients. These findings provide further evidence of a defect in the endothelium-derived nitric oxide system in hypertension and indicate that this abnormality is not related to decreased availability of substrate for nitric oxide production.
原发性高血压患者存在内皮源性一氧化氮系统缺陷，导致内皮依赖性血管舒张功能受损。本研究的目的是确定这种异常是否由一氧化氮合成底物缺乏所致。
在12名正常对照者（7名男性和5名女性；年龄49.3±7岁）和14名高血压患者（9名男性和5名女性；年龄48.4±7岁）中，联合给予5%葡萄糖或L-精氨酸（一氧化氮合成底物，以40μmol/min的速度输注）时，研究了对乙酰胆碱（一种内皮依赖性血管扩张剂，以7.5、15和30μg/min的速度输注）和硝普钠（一种直接作用于平滑肌的血管扩张剂，以0.8、1.6和3.2μg/min的速度输注）的血管反应。此外，在8名正常对照者和7名高血压患者中，研究了D-精氨酸（精氨酸的立体异构体，不是一氧化氮的前体）对乙酰胆碱血管反应的影响。将药物注入肱动脉，通过应变片体积描记法测量前臂血管系统的反应。与正常对照者相比，高血压患者对乙酰胆碱的血管扩张反应明显减弱（最大血流量分别为8.9±5和15.7±6 mL·min⁻¹·100 mL⁻¹；p<0.007）；然而，对硝普钠的反应未观察到差异（分别为11.4±6和11.7± mL·min⁻¹·100 mL⁻¹）。L-精氨酸在两组中均未显著改变基础血流量或血管阻力。在正常对照者中，输注L-精氨酸显著增强了对乙酰胆碱的血管扩张反应（L-精氨酸前后最大血流量分别为15.7±6和21.4±8 mL·min⁻¹·100 mL⁻¹；p<0.001）。相反，在高血压患者中，输注L-精氨酸并未改变对乙酰胆碱的反应（L-精氨酸前后最大血流量分别为8.9±5和8.4±4 mL·min⁻¹·100 mL⁻¹）。L-精氨酸的给药在两组中均未改变对硝普钠的反应。同样，输注D-精氨酸在两组中均未改变对乙酰胆碱的反应。
在正常人体内，一氧化氮生成底物的可用性是内皮依赖性血管舒张的限速步骤。相反，一氧化氮前体可用性的增加并未改变高血压患者内皮介导的血管舒张。这些发现进一步证明了高血压患者内皮源性一氧化氮系统存在缺陷，并表明这种异常与一氧化氮生成底物可用性降低无关。
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