Role of increased alpha 1-adrenergic activity in cardiomyopathic Syrian hamster.
We investigated serial changes in myocardial norepinephrine content and myocardial adrenergic receptors during the development of cardiomyopathy in Syrian hamsters (Bio 14.6) and their age-matched healthy controls. We also examined phosphatidylinositide hydrolysis after alpha 1-adrenergic stimulation and the effects of alpha 1-blockade. We found that in the prehypertrophic stage, myocardial norepinephrine content and densities of alpha 1- and beta-adrenergic receptors were significantly higher in the cardiomyopathic hamsters than in the controls. However, in the early heart failure stage, beta-receptor density was 28% lower than that of the age-matched controls, although alpha 1-receptor density remained 55% higher. Norepinephrine-stimulated phosphatidylinositide hydrolysis in the cardiomyopathic hamster in the hypertrophic stage was twice that in the controls, indicating that the increase in alpha 1-adrenergic receptors is coupled with the intracellular signal transduction. Furthermore, selective alpha 1-adrenoceptor blockade by bunazosin in the cardiomyopathic hamsters from 70 to 170 days of age reduced myocardial hypertrophy and focal myocardial necrosis. Thus we conclude that increased alpha 1-adrenergic activity plays an important role in progression of cardiac hypertrophy is cardiomyopathic Syrian hamsters.
Kagiya
T
T
First Department of Medicine, Osaka University Medical School Japan.
Hori
M
M
Iwakura
K
K
Iwai
K
K
Watanabe
Y
Y
Uchida
S
S
Yoshida
H
H
Kitabatake
A
A
Inoue
M
M
Kamada
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009202:Cardiomyopathies / Q000503:physiopathology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology; D006868:Hydrolysis; D008647:Mesocricetus; D009206:Myocardium / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D009638:Norepinephrine / Q000032:analysis / Q000097:blood; D009929:Organ Size / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D010716:Phosphatidylinositols; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C018176:bunazosin; D009638:Norepinephrine