Exercise training and β-blocker treatment ameliorate age-dependent impairment of β-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation
Exercise training and β-blocker treatment ameliorate age-dependent impairment of β-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation
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DOI：
10.1152/ajpheart.00308.2007
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发表时间：
2007-09-01
影响因子：
4.8
通讯作者：
Rengo, Franco
中科院分区：
文献类型：
--
作者：
Leosco, Dario;Rengo, Giuseppe;Rengo, Franco
Cardiac beta-adrenergic receptor (beta-AR) signaling and left ventricular (LV) responses to beta-AR stimulation are impaired with aging. It is shown that exercise and beta-AR blockade have a favorable effect on cardiac and vascular beta-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on beta-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise ( 12 wk treadmill training), metoprolol ( 250 mg . kg (-1) . day (-1) for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprolol-treated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to beta-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane beta-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac beta-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-protein-receptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of beta-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and beta-AR blockade can similarly ameliorate beta-AR signaling in the aged heart, leading to improved beta-AR responsiveness and corresponding LV inotropic reserve.
