EFFECT OF INCREASED AVAILABILITY OF NITRIC OXIDE PRECURSOR IN HYPERTENSION

我们之前已经证明，患有高血压的患者有 内皮依赖性血管松弛受损。在一个单独的 调查表明，前体的可获得性增加 因为内皮衍生的一氧化氮是限速性的，可以增强 正常人对内皮依赖性血管扩张剂的反应。 目前的研究是为了确定是否异常 高血压病患者内皮依赖性血管松弛可 通过增加一氧化氮底物的可用性来进行修饰。至 为此，14名高血压患者(年龄48岁+/-7岁；9名男性和5名 女性)进行了动脉内注射乙酰胆碱的研究 (内皮依赖性血管扩张剂)和硝普钠(直接的 血管扩张剂)输注L-精氨酸前后， 产生内皮源性一氧化氮的天然底物 氧化物。结果与对照组的结果进行了比较 12名正常志愿者(年龄49岁+/-7岁；7男5女)匹配 患者的年龄和性别。如前所述，血管扩张剂 比较高血压患者对乙酰胆碱的反应迟钝 对对照组；然而，没有观察到对 硝普钠。L-精氨酸的输注没有产生任何 高血压患者基础血流量的显著变化 或正常对照组。与正常对照组相比，L的输液- 精氨酸不能改变对乙酰胆碱的血管扩张反应。 同样，对硝普钠的反应也没有被L改变-- 精氨酸。这些发现表明，异常的内皮- 高血压患者的依赖性血管扩张功能不是由于降低所致 一氧化氮底物的可获得性，并进一步表明 内皮细胞合成或释放一氧化氮。

We have previously shown that patients with essential hypertension have impaired endothelium-dependent vascular relaxation. In a separate investigation, we demonstrated that increased availability of precursor for endothelium-derived nitric oxide is rate-limiting and can potentiate the response to endothelium-dependent vasodilators in normal humans. The present study was undertaken to determine whether the abnormal endothelium-dependent vascular relaxation of hypertensive patients can be modified by increasing availability of nitric oxide substrate. To this purpose, 14 hypertensive patients (age 48 +/- 7 years; 9 men and 5 women) were studied with intra-arterial infusion of acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle vasodilator) before and after the infusion of L-Arginine, the natural substrate for production of endothelium-derived nitric oxide. The results were compared with those obtained in a control group of 12 normal volunteers (age 49 +/- 7 years; 7 men and 5 women) matched to the patients for age and sex. As shown previously, the vasodilator response to acetylcholine was blunted in hypertensive patients compared to controls; however, no difference was observed in the response to sodium nitroprusside. The infusion of L-Arginine did not produce any significant change in basal blood flow in either hypertensive patients or normal controls. In contrast to normal controls, the infusion of L- Arginine did not modify the vasodilator response to acetylcholine. Similarly, the response to sodium nitroprusside was not altered by L- Arginine. These findings indicate that the abnormal endothelium- dependent vasodilation of hypertensive patients is not due to decreased nitric oxide substrate availability, and further suggest a defect in the synthesis or release of nitric oxide by endothelial cells.