title: Role of increased alpha 1-adrenergic activity in cardiomyopathic Syrian hamster.
abstract: 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.
authors.affiliation: First Department of Medicine, Osaka University Medical School Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kagiya
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Iwakura
authors.forename: K
authors.initials: K
authors.lastname: Iwai
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Uchida
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: A
authors.initials: A
authors.lastname: Kitabatake
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Kamada
mesh_terms: 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
chemical_list: D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D010716:Phosphatidylinositols; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C018176:bunazosin; D009638:Norepinephrine