Impaired gene expression of beta 1-adrenergic receptor, but not stimulatory G-protein Gs alpha, in rat ventricular myocardium treated with isoproterenol.
We investigated the gene expression of beta(1)-adrenergic receptor (beta(1)AR) and stimulatory G-protein Gsalpha, important signal transduction elements for regulating heart rate and contractility, in ventricle after chronic treatment with isoproterenol (ISO) in rat. Rats were treated with ISO (4 mg/kg, intraperitoneal) twice a day for 4 d. Ventricle weight of the heart and ventricle weight/body weight ratio were increased by 23% and 25% compared with control, respectively. Positive inotropic responses to ISO in left atrial muscle preparations isolated from ISO-treated rats were markedly decreased. Northern blot hybridization showed that the mRNA transcript of beta(1)AR was significantly decreased in ventricle of ISO-treated rats, whereas Gsalpha mRNA level was unchanged. Present results demonstrate that the gene expression of myocardial beta(1)AR, but not Gsalpha, was decreased in rat myocardium of ISO-induced cardiac hypertrophy, and suggesting that decrease in the gene expression of beta(1)AR may be one of the mechanisms responsible for the diminished cardiac function.
Kizaki
Keiichiro
K
Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Japan. kizaki@vmas.kitasato-u.ac.jp
Momozaki
Masami
M
Akatsuka
Keiko
K
Fujimori
Yuuki
Y
Uchide
Tsuyoshi
T
Temma
Kyosuke
K
Hara
Yukio
Y
D058665:Adrenergic beta-1 Receptor Agonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000096:biosynthesis* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis* / Q000235:genetics*
D058665:Adrenergic beta-1 Receptor Agonists; D018342:Receptors, Adrenergic, beta-1; D019205:GTP-Binding Protein alpha Subunits, Gs; D007545:Isoproterenol