Moreno H, Chalon S, Urae A, Tangphao O, Abiose A K, Hoffman B B, Blaschke T F
Division of Clinical Pharmacology, Department of Medicine, Stanford University School of Medicine, Stanford 94305-5130, USA.
Am J Physiol. 1998 Sep;275(3):H1040-5. doi: 10.1152/ajpheart.1998.275.3.H1040.
Cigarette smoking has been shown to impair endothelium-dependent dilation in arteries. We tested the hypothesis that cigarette smoking also impairs endothelium-dependent venodilation and evaluated changes in this response after smoking cessation in a time-course study using the dorsal hand vein technique. Dose-response curves were constructed in smokers and nonsmokers by infusing bradykinin (1-278 ng/min), an endothelium-dependent vasodilator, and nitroglycerin (0.006-1,583 ng/min), an endothelium-independent vasodilator, into hand veins preconstricted with the selective alpha1-adrenergic agonist phenylephrine. The maximal venodilation induced by bradykinin was 89 +/- 5% in controls (n = 16) and 61 +/- 7% in smokers (n = 18; P = 0.02). No difference in nitroglycerin-induced venodilation was observed between the two groups. Coinfusion of L-arginine (0.33 mg/min) markedly improved the bradykinin-induced venodilation in smokers (52 +/- 7 to 90 +/- 9%; P < 0.01). After acute smoking cessation (n = 7), restoration to normal bradykinin-induced venodilation was observed within 24 h, whereas no change in the response to a maximally effective dose of nitroglycerin (1,583 ng/min) was detected. In a human vein model appropriate for testing vascular functional alterations, this study demonstrates that smoking impairs endothelium-dependent venodilation in heavy smokers. Moreover, this endothelial dysfunction appears to be rapidly reversible after smoking cessation. This model may be useful in studies evaluating mechanisms of endothelial dysfunction and interventions to modify it.
吸烟已被证明会损害动脉中内皮依赖性舒张功能。我们检验了这样一个假设，即吸烟也会损害内皮依赖性静脉舒张功能，并在一项使用手背静脉技术的时间进程研究中评估了戒烟后这种反应的变化。通过向预先用选择性α1-肾上腺素能激动剂去氧肾上腺素收缩的手部静脉中注入缓激肽（1 - 278 ng/分钟）（一种内皮依赖性血管舒张剂）和硝酸甘油（0.006 - 1583 ng/分钟）（一种非内皮依赖性血管舒张剂），构建吸烟者和非吸烟者的剂量反应曲线。缓激肽诱导的最大静脉舒张在对照组（n = 16）中为89±5%，在吸烟者（n = 18；P = 0.02）中为61±7%。两组之间硝酸甘油诱导的静脉舒张没有差异。同时注入L-精氨酸（0.33 mg/分钟）可显著改善吸烟者中缓激肽诱导的静脉舒张（从52±7%提高到90±9%；P < 0.01）。急性戒烟后（n = 7），在24小时内观察到缓激肽诱导的静脉舒张恢复正常，而对最大有效剂量硝酸甘油（1583 ng/分钟）的反应没有变化。在一个适合测试血管功能改变的人体静脉模型中，本研究表明吸烟会损害重度吸烟者的内皮依赖性静脉舒张功能。此外，这种内皮功能障碍在戒烟后似乎可迅速逆转。该模型可能有助于评估内皮功能障碍机制及改善内皮功能障碍干预措施的研究。
