Kobayashi A, Nishiyama T, Ikegaya T, Kaneko M, Yamazaki N
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Mol Cell Biochem. 1993 Apr 7;121(1):59-65. doi: 10.1007/BF00928700.
In general, it is recognized that prolonged exposure to catecholamine leads to a reduction in the beta-adrenoceptor density (downregulation). However, it has been previously reported that the myocardial beta-adrenoceptor densities and norepinephrine levels significantly increase in the hearts of BIO 14.6 cardiomyopathic hamsters in the early stage. The mechanism of the increased beta-adrenoceptor density is not clearly elucidated, and it can not be excluded that this phenomenon may be a secondary effect. The purpose of this study was to assess the effect of verapamil on the density of beta-adrenoceptors in the heart of BIO 14.6 cardiomyopathic hamsters. The total number of beta-adrenoceptors in untreated BIO 14.6 hamsters was significantly higher at 90 days of age (30.4 +/- 2.2 v.s. 25.9 +/- 1.4 fmol/mg protein, p < 0.05). BIO 14.6 hamsters received daily intraperitoneal injections of 5 mg/kg verapamil for 70 days, from an age of 20 days. Verapamil protected against progressive myocardial damage (total damage; 8.2 +/- 0.7 v.s. 0.4 +/- 0.2%/area, p < 0.05) and the myocardial beta-adrenoceptor density returned to that of the normal control group (26.9 +/- 3.0 fmol/mg protein). Conversely, verapamil did not have an effect on the number of myocardial beta-adrenoceptors in normal golden hamsters. This study showed that verapamil protected against progressive myocardial damage and myocardial beta-adrenoceptor density returned to those of normal hamsters. These results suggest that an increased number of beta-adrenoceptors in the early stage of BIO 14.6 cardiomyopathic hamsters may be involved in the secondary pathogenesis of cardiomyopathy.
一般认为，长期暴露于儿茶酚胺会导致β-肾上腺素能受体密度降低（下调）。然而，此前有报道称，在早期阶段，BIO 14.6心肌病仓鼠心脏中的心肌β-肾上腺素能受体密度和去甲肾上腺素水平显著增加。β-肾上腺素能受体密度增加的机制尚未明确阐明，且不能排除这种现象可能是一种继发效应。本研究的目的是评估维拉帕米对BIO 14.6心肌病仓鼠心脏中β-肾上腺素能受体密度的影响。未经治疗的BIO 14.6仓鼠在90日龄时β-肾上腺素能受体总数显著更高（30.4±2.2对25.9±1.4 fmol/mg蛋白质，p<0.05）。从20日龄开始，BIO 14.6仓鼠每天腹腔注射5 mg/kg维拉帕米，持续70天。维拉帕米可预防进行性心肌损伤（总损伤；8.2±0.7对0.4±0.2%/面积，p<0.05），且心肌β-肾上腺素能受体密度恢复至正常对照组水平（26.9±3.0 fmol/mg蛋白质）。相反，维拉帕米对正常金黄仓鼠心肌β-肾上腺素能受体数量没有影响。本研究表明，维拉帕米可预防进行性心肌损伤且心肌β-肾上腺素能受体密度恢复至正常仓鼠水平。这些结果表明，BIO 14.6心肌病仓鼠早期β-肾上腺素能受体数量增加可能参与了心肌病的继发发病机制。
