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血管紧张素转换酶抑制和β受体阻滞剂对Bio 14.6仓鼠心脏胶原重塑的影响。

Effects of ACE inhibition and beta-blockade on collagen remodelling in the heart of Bio 14.6 hamsters.

作者信息

Mansoor A M, Honda M, Kuramochi T, Tanaka K, Morioka S, Takabatake T

机构信息

Department of Internal Medicine, Shimane Medical University, Izumo, Japan.

出版信息

Clin Exp Pharmacol Physiol. 1996 Jan;23(1):43-9. doi: 10.1111/j.1440-1681.1996.tb03060.x.

DOI:10.1111/j.1440-1681.1996.tb03060.x
PMID:8713495
Abstract
  1. The effects of angiotensin converting enzyme (ACE) inhibition and beta-blockade on collagen in the heart and on plasma catecholamines and tissue angiotensin (Ang) I and II were examined in Bio 14.6 Syrian hamsters. Male hamsters (76-79 days old) were given low-dose enalapril (3 mg/kg per day), high-dose enalapril (30 mg/kg per day), atenolol (50 mg/kg per day) or vehicle for 65 days. Age and sex matched healthy F1b hamsters were used as controls. Collagen concentration was determined by measuring hydroxyproline content and the relative proportion of type I, III, and V collagens was obtained by non-interrupted sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). Per cent collagen area (PCA) was measured by pixel counting in myocardial tissue by a personal computer. 2. Although heartweight (HW) and bodyweight (BW) in F1b controls were significantly higher compared with drug-treated groups and vehicles, the HW/BW ratio in cardiomyopathic Bio 14.6 hamsters tended to be high compared with F1b controls and was decreased by each drug treatment. 3. Collagen concentration, total collagen content and PCA in the heart of Bio 14.6 hamsters were significantly higher than F1b controls. Collagen concentration and total collagen content were significantly decreased in all drug-treated groups compared with vehicles. 4. The proportion of type I collagen tended to decrease while that of type III collagen tended to increase in all drug-treated groups compared with vehicles. Type V collagen in vehicle-treated group was significantly higher than in F1b controls, while it tended to decrease in all drug-treated groups compared with vehicles. 5. Plasma concentrations of catecholamines (adrenaline and noradrenaline) were decreased significantly by atenolol and high-dose enalapril, but not by low-dose enalapril. Tissue AngI remained unaltered in any of the drug-treated hamsters. Tissue AngII was decreased by the high-dose enalapril and beta-blockade, and tended to be decreased by low-dose enalapril treatment. 6. These results reveal that enalapril and atenolol produced similar beneficial effects on collagen remodelling in Bio 14.6 hamsters by decreasing the total amount of collagen, and also by changing collagen phenotypes through the inhibition of the renin-angiotensin system. Both drugs also improved myocardial morphological integrity.
摘要
  1. 在Bio 14.6叙利亚仓鼠中,研究了血管紧张素转换酶(ACE)抑制和β受体阻滞剂对心脏胶原蛋白、血浆儿茶酚胺以及组织血管紧张素(Ang)I和II的影响。雄性仓鼠(76 - 79日龄)接受低剂量依那普利(3毫克/千克/天)、高剂量依那普利(30毫克/千克/天)、阿替洛尔(50毫克/千克/天)或赋形剂处理65天。年龄和性别匹配的健康F1b仓鼠用作对照。通过测量羟脯氨酸含量来测定胶原蛋白浓度,并通过非间断十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS - PAGE)获得I型、III型和V型胶原蛋白的相对比例。通过个人计算机对心肌组织进行像素计数来测量胶原蛋白面积百分比(PCA)。2. 虽然F1b对照组的心脏重量(HW)和体重(BW)显著高于药物治疗组和赋形剂组,但与F1b对照组相比,心肌病Bio 14.6仓鼠的HW/BW比值往往较高,且每种药物治疗均可使其降低。3. Bio 14.6仓鼠心脏中的胶原蛋白浓度、总胶原蛋白含量和PCA均显著高于F1b对照组。与赋形剂组相比,所有药物治疗组的胶原蛋白浓度和总胶原蛋白含量均显著降低。4. 与赋形剂组相比,所有药物治疗组中I型胶原蛋白的比例趋于降低,而III型胶原蛋白的比例趋于增加。赋形剂处理组的V型胶原蛋白显著高于F1b对照组,而与赋形剂组相比,所有药物治疗组中V型胶原蛋白均趋于降低。5. 阿替洛尔和高剂量依那普利可显著降低血浆儿茶酚胺(肾上腺素和去甲肾上腺素)浓度,但低剂量依那普利无此作用。在任何药物治疗的仓鼠中,组织AngI均未改变。高剂量依那普利和β受体阻滞剂可降低组织AngII,低剂量依那普利治疗也使其有降低趋势。6. 这些结果表明,依那普利和阿替洛尔通过减少胶原蛋白总量以及通过抑制肾素 - 血管紧张素系统改变胶原蛋白表型,对Bio 14.6仓鼠的胶原蛋白重塑产生了相似的有益作用。两种药物还改善了心肌形态完整性。

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