Verapamil induced reduction of the myocardial beta-adrenoceptor density in BIO 14.6 cardiomyopathic Syrian hamsters.
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.
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
A
A
Kobayashi
T
T
Nishiyama
T
T
Ikegaya
M
M
Kaneko
N
N
Yamazaki
D000818:Animals; D001667:Binding, Competitive; D015220:Calcium Channels / Q000187:drug effects; D009202:Cardiomyopathies / Q000503:physiopathology* / Q000517:prevention & control; D006224:Cricetinae; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D010869:Pindolol; D014700:Verapamil