論文 - 詳細
| RRC ID | 194 |
|---|---|
| 著者 | Tsuneyoshi H, Oriyanhan W, Kanemitsu H, Shiina R, Nishina T, Matsuoka S, Ikeda T, Komeda M. |
| タイトル | Does the beta2-agonist clenbuterol help to maintain myocardial potential to recover during mechanical unloading? |
| ジャーナル | Circulation |
| Abstract |
OBJECTIVE:Chronic mechanical unloading induces left ventricular (LV) atrophy, which may impair functional recovery during support with an LV-assist device. Clenbuterol, a beta2-adrenergic receptor (AR) agonist, is known to induce myocardial hypertrophy and might prevent LV atrophy during LV unloading. Furthermore, beta2-AR stimulation is reported to improve Ca2+ handling and contribute to antiapoptosis. However, there is little information on the effects of clenbuterol during LV unloading. METHODS AND RESULTS:We investigated LV atrophy and function after LV unloading produced by heterotopic heart transplantation in isogenic rats. After transplantation, rats were randomized to 1 of 2 groups (n=10 each). The clenbuterol group received 2 mg.kg(-1).d(-1) of the drug for 2 weeks; the control group received normal saline. The weight of unloaded control hearts was 48% less than that of host hearts after 2 weeks of unloading. Clenbuterol significantly increased the weight of the host hearts but did not prevent unloading-induced LV atrophy. Papillary muscles were isolated and stimulated, and there was no difference in developed tension between the 2 groups. However, the inotropic response to the beta-AR agonist isoproterenol significantly improved in the clenbuterol group. The mRNA expression of myocardial sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) and fetal gene shift (myosin heavy chain [MHC] mRNA isozyme) was also significantly improved by clenbuterol treatment. There was no difference in beta1-AR mRNA expression between the 2 groups. In contrast, beta2-AR mRNA was significantly decreased in the clenbuterol-treated, unloaded heart. This indicates that clenbuterol may downregulate beta2-ARs. In the evaluation of apoptosis, mRNA expression of caspase-3, which is the central pathway for apoptosis, tended to be better in the clenbuterol group. CONCLUSIONS:During complete LV unloading, clenbuterol did not prevent myocardial atrophy but improved gene expression (SERCA2a, beta-MHC) and beta-adrenergic responsiveness and potentially prevented myocardial apoptosis. However, chronic administration of clenbuterol may be associated with downregulation of beta2-ARs. |
| 巻・号 | 112(9 Suppl) |
| ページ | I51-6 |
| 公開日 | 2005-8-30 |
| DOI | 10.1161/CIRCULATIONAHA.104.525097 |
| PII | 112/9_suppl/I-51 |
| PMID | 16159865 |
| MeSH | Adrenergic beta-Agonists / pharmacology Adrenergic beta-Agonists / therapeutic use* Animals Atrophy Calcium-Transporting ATPases / biosynthesis Calcium-Transporting ATPases / genetics Caspase 3 Caspases / biosynthesis Caspases / genetics Clenbuterol / pharmacology Clenbuterol / therapeutic use* Down-Regulation / drug effects Drug Evaluation, Preclinical Enzyme Induction / drug effects Gene Expression Regulation / drug effects Heart / drug effects* Heart Transplantation Heart Ventricles / drug effects Heart Ventricles / pathology Heart Ventricles / physiopathology Isoproterenol / pharmacology Male Myocardial Contraction / drug effects Myocardium / pathology Myosin Heavy Chains / biosynthesis Myosin Heavy Chains / genetics Organ Size Papillary Muscles / drug effects Papillary Muscles / physiopathology Protein Isoforms / biosynthesis Protein Isoforms / genetics RNA, Messenger / biosynthesis RNA, Messenger / genetics Random Allocation Rats Rats, Inbred Lew Receptors, Adrenergic, beta-1 / biosynthesis Receptors, Adrenergic, beta-1 / genetics Receptors, Adrenergic, beta-2 / biosynthesis Receptors, Adrenergic, beta-2 / drug effects Receptors, Adrenergic, beta-2 / genetics Sarcoplasmic Reticulum Calcium-Transporting ATPases Stress, Mechanical Transplantation, Heterotopic Transplantation, Isogeneic Ventricular Function, Left / drug effects |
| IF | 23.603 |
| 引用数 | 27 |
| WOS 分野 | CARDIAC & CARDIOVASCULAR SYSTEMS PERIPHERAL VASCULAR DISEASE |
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