Exercise training and β-blocker treatment ameliorate age-dependent impairment of β-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation

Dario Leosco, Giuseppe Rengo, Guido Iaccarino, Amelia Filippelli, Anastasios Lymperopoulos, Carmela Zincarelli, Francesca Fortunato, Luca Golino, Massimo Marchese, Giovanni Esposito, Antonio Rapacciuolo, Barbara Rinaldi, Nicola Ferrara, Walter J. Koch, Franco Rengo

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiac β-adrenergic receptor (β-AR) signaling and left ventricular (LV) responses to β-AR stimulation are impaired with aging. It is shown that exercise and β-AR blockade have a favorable effect on cardiac and vascular β-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on β-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 β-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane β-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac β-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 β-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and β-AR blockade can similarly ameliorate β-AR signaling in the aged heart, leading to improved β-AR responsiveness and corresponding LV inotropic reserve.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number3
DOIs
Publication statusPublished - Sep 2007

Keywords

  • β-adrenergic receptor desensitization
  • Aging
  • G-protein-coupled receptor kinase 2
  • Heart failure

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Exercise training and β-blocker treatment ameliorate age-dependent impairment of β-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation'. Together they form a unique fingerprint.

Cite this