Berkenboom G, Unger P, Fontaine J
Cardiology Department, Erasmus Hospital, Brussels, Belgium.
J Cardiovasc Pharmacol. 1989;14 Suppl 11:S35-9.
In canine and porcine coronary arteries, experimental atherosclerosis (induced by endothelial denudation followed by a high-cholesterol diet) potentiates the vasoconstrictor effects of histamine, serotonin, and ergonovine. In isolated human atherosclerotic coronary arteries, only hypersensitivity to histamine has been demonstrated. This discrepancy could be due to several factors. First, the atherosclerotic lesions in human vessels are different from those observed in the animal, since experimental atherosclerosis often corresponds only to the early stage of the disease in humans. Second, the human atherosclerotic coronary arteries were isolated mainly from patients with cardiac failure, a condition that alters the responses of coronary smooth muscle to vasoactive amines. With regard to endothelium-dependent vasodilators, marked attenuations of the relaxations to substance P, bradykinin, and the Ca2+ ionophore A23187 have been described in isolated human atherosclerotic arteries. Acetylcholine elicits variable responses in these preparations and even if the arteries are devoid of atherosclerotic lesions, it often fails to relax them. In addition to this endothelial dysfunction, severely atherosclerotic human coronary vessels exhibit a slightly decreased responsiveness to nitroglycerin and SIN-1 but not to forskolin. Another abnormality of the smooth muscle is a marked attenuated beta-adrenergic relaxation. Thus, atherosclerosis of human coronary vessels induces not only marked alterations in endothelium-dependent responses but also modifies the sensitivity to several endothelium-independent vasodilators.
在犬类和猪的冠状动脉中，实验性动脉粥样硬化（通过内皮剥脱后给予高胆固醇饮食诱导）会增强组胺、5-羟色胺和麦角新碱的血管收缩作用。在分离出的人类动脉粥样硬化冠状动脉中，仅证实了对组胺过敏。这种差异可能归因于几个因素。首先，人类血管中的动脉粥样硬化病变与动物中观察到的不同，因为实验性动脉粥样硬化通常仅相当于人类疾病的早期阶段。其次，人类动脉粥样硬化冠状动脉主要从心力衰竭患者中分离出来，这种情况会改变冠状动脉平滑肌对血管活性胺的反应。关于内皮依赖性血管舒张剂，在分离出的人类动脉粥样硬化动脉中，已描述了对P物质、缓激肽和Ca2+离子载体A23187的舒张反应明显减弱。乙酰胆碱在这些制剂中引发可变反应，即使动脉没有动脉粥样硬化病变，它也常常无法使其舒张。除了这种内皮功能障碍外，严重动脉粥样硬化的人类冠状动脉对硝酸甘油和SIN-1的反应略有降低，但对福斯可林的反应没有降低。平滑肌的另一个异常是β-肾上腺素能舒张明显减弱。因此，人类冠状动脉的动脉粥样硬化不仅会引起内皮依赖性反应的明显改变，还会改变对几种内皮非依赖性血管舒张剂的敏感性。
