Panza J A, Quyyumi A A, Brush J E, Epstein S E
Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md. 20892.
N Engl J Med. 1990 Jul 5;323(1):22-7. doi: 10.1056/NEJM199007053230105.
Endothelium regulates vascular tone by influencing the contractile activity of vascular smooth muscle. This regulatory effect of the endothelium on blood vessels has been shown to be impaired in atherosclerotic arteries in humans and animals and in animal models of hypertension.
To determine whether patients with essential hypertension have an endothelium-dependent abnormality in vascular relaxation, we studied the response of the forearm vasculature to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in 18 hypertensive patients (mean age [+/- SD], 50.7 +/- 10 years; 10 men and 8 women) two weeks after the withdrawal of antihypertensive medications and in 18 normal controls (mean age, 49.9 +/- 9; 9 men and 9 women). The drugs were infused at increasing concentrations into the brachial artery, and the response in forearm blood flow was measured by strain-gauge plethysmography.
The basal forearm blood flow was similar in the patients and controls (mean +/- SD, 3.4 +/- 1.3 and 3.7 +/- 0.8 ml per minute per 100 ml of forearm tissue, respectively; P not significant). The responses of blood flow and vascular resistance to acetylcholine were significantly reduced in the hypertensive patients (P less than 0.0001); maximal forearm flow was 9.1 +/- 5 ml per minute per 100 ml in the patients and 20.0 +/- 8 ml per minute per 100 ml in the controls (P less than 0.0002). However, there were no significant differences between groups in the responses of blood flow and vascular resistance to sodium nitroprusside. Because the vasodilator effect of acetylcholine might also be due to presynaptic inhibition of the release of norepinephrine by adrenergic nerve terminals, the effect of acetylcholine was assessed during phentolamine-induced alpha-adrenergic blockade. Under these conditions, it was also evident that the responses to acetylcholine were significantly blunted in the hypertensive patients (P less than 0.03).
Endothelium-mediated vasodilation is impaired in patients with essential hypertension. This defect may play an important part in the functional abnormalities of resistance vessels that are observed in hypertensive patients.
内皮通过影响血管平滑肌的收缩活动来调节血管张力。在人类和动物的动脉粥样硬化动脉以及高血压动物模型中，内皮对血管的这种调节作用已被证明受损。
为了确定原发性高血压患者是否存在血管舒张的内皮依赖性异常，我们研究了18例高血压患者（平均年龄[±标准差]，50.7±10岁；10名男性和8名女性）在停用抗高血压药物两周后以及18名正常对照者（平均年龄，49.9±9岁；9名男性和9名女性）的前臂血管对乙酰胆碱（一种内皮依赖性血管扩张剂）和硝普钠（一种平滑肌直接扩张剂）的反应。将药物以递增浓度注入肱动脉，并通过应变片体积描记法测量前臂血流的反应。
患者和对照者的基础前臂血流相似（平均±标准差，分别为每分钟每100毫升前臂组织3.4±1.3和3.7±0.8毫升；P无显著性差异）。高血压患者对乙酰胆碱的血流和血管阻力反应显著降低（P<0.0001）；患者的最大前臂血流为每分钟每100毫升9.1±5毫升，对照者为每分钟每100毫升20.0±8毫升（P<0.0002）。然而，两组对硝普钠的血流和血管阻力反应无显著差异。由于乙酰胆碱的血管扩张作用也可能归因于肾上腺素能神经末梢对去甲肾上腺素释放的突触前抑制，因此在酚妥拉明诱导的α-肾上腺素能阻滞期间评估了乙酰胆碱的作用。在这些条件下，高血压患者对乙酰胆碱的反应明显减弱也很明显（P<0.03）。
原发性高血压患者内皮介导的血管舒张受损。这种缺陷可能在高血压患者中观察到的阻力血管功能异常中起重要作用。
