Nabel E G, Ganz P, Gordon J B, Alexander R W, Selwyn A P
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Circulation. 1988 Jan;77(1):43-52. doi: 10.1161/01.cir.77.1.43.
Increased vascular constriction has been observed at the site of atherosclerotic lesions, suggesting an association between atherosclerosis and altered vascular tone. While atherosclerosis may increase sensitivity to exogenous vasoconstrictors, little is known about the response of normal and atherosclerotic coronary arteries to an exogenous stimulus that excites the sympathetic nervous system. Therefore, we studied the response to cold pressor test (CPT) using quantitative angiography and Doppler flow velocity measurements in eight patients with angiographically normal coronary arteries (group I), nine patients with mild coronary atherosclerosis (less than 50% diameter narrowing) (group II), and 13 patients with advanced coronary stenoses (greater than 50% diameter narrowing) (group III). In 31 segments of angiographically smooth arteries in group I, the CPT produced vasodilation from a control mean diameter of 2.68 +/- 0.09 (mean +/- SE) to 2.99 +/- 0.09 mm at peak CPT (p less than 0.001), a 12 +/- 1% increase in diameter. In group II, 27 irregular segments constricted to peak CPT from a mean control diameter of 1.82 +/- 0.12 to 1.66 +/- 0.12 mm (p less than .001), a 9 +/- 1% decrease, while 10 smooth segments dilated from a mean control diameter of 1.98 +/- 0.11 mm to 2.34 +/- 0.15 mm (p less than .01), a 19 +/- 2% increase in diameter. Likewise, in group III, the 17 stenotic segments constricted from 1.16 +/- 0.09 to 0.89 +/- 0.09 mm (p less than .001), a 24 +/- 6% decrease; the irregular segments also constricted from 2.44 +/- 0.11 to 2.22 +/- 0.12 mm (p = .002), a 10 +/- 2% decrease. In contrast, two smooth segments dilated from 2.98 to 3.23 mm (mean), an 8% increase in diameter. Coronary blood flow increased 65 +/- 4% (mean) during CPT in group I, it increased 15 +/- 6% in group II, and it decreased 39 +/- 8% in group III. The vasodilator response in four normal patients was partly inhibited by the administration of intracoronary propranolol (17 +/- 3% increase during control, 10 +/- 2% increase after propranolol, 41% less dilation; p = .002). We conclude that the response of normal coronary arteries to the CPT test is dilation, in part related to beta-adrenoreceptor stimulation and possibly flow-mediated endothelial dilation or alpha 2-adrenergic activity. The paradoxical vasoconstrictor response induced by atherosclerosis may represent altered catecholamine sensitivity and/or a defect in endothelial vasodilator function. The presence of atherosclerosis impairs vasodilator responses and thus may contribute to the pathogenesis of myocardial ischemia.
在动脉粥样硬化病变部位观察到血管收缩增强，这表明动脉粥样硬化与血管张力改变之间存在关联。虽然动脉粥样硬化可能会增加对外源性血管收缩剂的敏感性，但对于正常和动脉粥样硬化的冠状动脉对外源性刺激（激发交感神经系统）的反应知之甚少。因此，我们使用定量血管造影和多普勒流速测量方法，研究了8例冠状动脉造影正常的患者（I组）、9例轻度冠状动脉粥样硬化（直径狭窄小于50%）的患者（II组）和13例严重冠状动脉狭窄（直径狭窄大于50%）的患者（III组）对冷加压试验（CPT）的反应。在I组造影显示光滑的31段动脉中，CPT使平均直径从对照时的2.68±0.09（平均值±标准误）毫米扩张至CPT峰值时的2.99±0.09毫米（p<0.001），直径增加了12±1%。在II组中，27段不规则动脉从平均对照直径1.82±0.12毫米收缩至CPT峰值时的1.66±0.12毫米（p<0.001），直径减少了9±1%，而10段光滑动脉从平均对照直径1.98±0.11毫米扩张至2.34±0.15毫米（p<0.01），直径增加了19±2%。同样，在III组中，17段狭窄动脉从1.16±0.09毫米收缩至0.89±0.09毫米（p<0.001），直径减少了24±6%；不规则动脉也从2.44±0.11毫米收缩至2.22±0.12毫米（p = 0.002），直径减少了10±2%。相比之下，2段光滑动脉从2.98毫米扩张至3.23毫米（平均值），直径增加了8%。I组CPT期间冠状动脉血流量平均增加65±4%，II组增加15±6%，III组减少39±8%。4例正常患者的血管扩张反应部分被冠状动脉内给予普萘洛尔所抑制（对照期间增加17±3%，普萘洛尔后增加10±2%，扩张减少41%；p = 0.002）。我们得出结论，正常冠状动脉对CPT试验的反应是扩张，部分与β-肾上腺素能受体刺激有关，可能还与血流介导的内皮舒张或α2-肾上腺素能活性有关。动脉粥样硬化引起的矛盾性血管收缩反应可能代表儿茶酚胺敏感性改变和/或内皮舒张功能缺陷。动脉粥样硬化的存在损害了血管舒张反应，因此可能促成心肌缺血的发病机制。
