Cardillo C, Kilcoyne C M, Cannon R O, Panza J A
Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
J Am Coll Cardiol. 1998 Nov;32(5):1207-13. doi: 10.1016/s0735-1097(98)00391-x.
This study investigated whether mental stress-induced vasodilation mediated by endothelium-derived nitric oxide (NO) is defective in conditions with endothelial dysfunction, such as hypertension and hypercholesterolemia.
Vascular release of NO modulates the vasodilator response to mental stress in healthy subjects. Previous studies have shown that hypertensive and hypercholesterolemic patients have impaired endothelium-dependent vasodilation to pharmacologic agents due to decreased NO activity. However, whether this abnormality also operates in response to physiologic stimuli such as mental stress has not been defined.
Forearm blood flow responses (plethysmography) to mental stress were compared in 12 normal subjects, 12 hypertensive patients and 10 hypercholesterolemic patients before and during NO synthesis inhibition with N(G)-monomethyl-L-arginine (4 micromol/min). Vascular responses to acetylcholine (7.5, 15 and 30 microg/min), an endothelium-dependent vasodilator, and sodium nitroprusside (0.8, 1.6 and 3.2 microg/min), an exogenous NO donor, were also assessed in each group.
During saline the vasodilator response to mental stress was significantly blunted in hypertensive (37+/-11%; p=0.01) but not in hypercholesterolemic (85+/-21%; p=0.78) patients compared with controls (93+/-15%). N(G)-Monomethyl-L-arginine administration significantly blunted mental stress-induced vasodilation in healthy subjects (p=0.004 vs. saline) and hypercholesterolemic patients (p=0.03 vs. saline), but not in hypertensive patients (p=0.69 vs. saline). The vasodilator effect of the highest dose of acetylcholine was similarly blunted in hypertensive (215+/-44%; p=0.02) and hypercholesterolemic (172+/-71%; p=0.02) patients compared with controls (364+/-34), whereas the vasorelaxing response to sodium nitroprusside was similar in the three groups.
Hypertensive but not hypercholesterolemic patients have impaired NO-dependent vasodilation during mental stress. These findings may be accounted for by different mechanisms underlying endothelial dysfunction in these two conditions and might explain an increased susceptibility of hypertensive patients to vascular damage over repeated exposure to stressful situations.
本研究调查了在诸如高血压和高胆固醇血症等存在内皮功能障碍的情况下，由内皮衍生的一氧化氮（NO）介导的精神应激诱导的血管舒张是否存在缺陷。
在健康受试者中，NO的血管释放调节对精神应激的血管舒张反应。先前的研究表明，高血压和高胆固醇血症患者由于NO活性降低，对药物制剂的内皮依赖性血管舒张受损。然而，这种异常是否也在诸如精神应激等生理刺激的反应中起作用尚未明确。
在12名正常受试者、12名高血压患者和10名高胆固醇血症患者中，比较了在使用N(G)-单甲基-L-精氨酸（4微摩尔/分钟）抑制NO合成之前和期间，前臂血流对精神应激的反应（体积描记法）。还评估了每组对内皮依赖性血管舒张剂乙酰胆碱（7.5、15和30微克/分钟）和外源性NO供体硝普钠（0.8、1.6和3.2微克/分钟）的血管反应。
与对照组（93±15%）相比，在输注生理盐水期间，高血压患者（37±11%；p=0.01）对精神应激的血管舒张反应明显减弱，但高胆固醇血症患者（85±21%；p=0.78）没有。给予N(G)-单甲基-L-精氨酸后，健康受试者（与输注生理盐水相比，p=0.004）和高胆固醇血症患者（与输注生理盐水相比，p=0.03）中精神应激诱导的血管舒张明显减弱，但高血压患者中没有（与输注生理盐水相比，p=0.69）。与对照组（364±34）相比，高血压患者（215±44%；p=0.02）和高胆固醇血症患者（172±71%；p=0.02）中最高剂量乙酰胆碱的血管舒张作用同样减弱，而三组对硝普钠的血管舒张反应相似。
高血压患者而非高胆固醇血症患者在精神应激期间存在NO依赖性血管舒张受损。这些发现可能由这两种情况下内皮功能障碍的不同机制所解释，并且可能解释了高血压患者在反复暴露于应激情况时对血管损伤的易感性增加。
