Boucek R J, Gunja-Smith Z, Noble N L, Simpson C F
Biochem Pharmacol. 1983 Jan 15;32(2):275-80. doi: 10.1016/0006-2952(83)90555-5.
dl-Propranolol (propranolol) fed to immature and mature aneurysm-prone turkeys (Broad-Breasted White, BBW) for 6 weeks significantly raised the tensile strength of tissue rings from the abdominal aorta. The drug-mediated increase in tensile strength values was dose-related and independent of its heart rate- and arterial pressure-lowering effects. Propranolol acts, in part, by (a) stimulating lysyl oxidase to produce greater amounts of reactive aldehydes for intermolecular cross-links, (b) enhancing the progression of chemically unstable to stable forms of intermolecular elastin cross-links (lysinonorleucine and the desmosines), and (c) reducing the density of the age-related intermolecular cross-linking of collagen (pyridinoline). These propranolol effects on the lysyl cross-links were demonstrated in both the immature and mature animals and suggest a heretofore unrecognized potential for this widely used cardiovascular drug.
给未成熟和成熟的易患动脉瘤火鸡(宽胸白羽火鸡,BBW)喂食消旋普萘洛尔(普萘洛尔)6周后,显著提高了腹主动脉组织环的抗张强度。药物介导的抗张强度值增加与剂量相关,且与其降低心率和动脉压的作用无关。普萘洛尔部分通过以下方式起作用:(a)刺激赖氨酰氧化酶产生更多用于分子间交联的反应性醛;(b)促进分子间弹性蛋白交联从化学不稳定形式向稳定形式(赖氨酰正亮氨酸和锁链素)的转变;(c)降低与年龄相关的胶原蛋白分子间交联(吡啶啉)的密度。普萘洛尔对赖氨酰交联的这些作用在未成熟和成熟动物中均得到证实,表明这种广泛使用的心血管药物具有此前未被认识到的潜力。