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1 The Noll Physiological Research Center
2 The Department of Kinesiology, The Pennsylvania State University, University Park.
3 Department of Kinesiology, Texas A&M University, College Station.
Address correspondence to Donna H. Korzick, PhD, 106 Noll Physiological Research Center, The Pennsylvania State University, University Park, PA 16802. E-mail: dhk102{at}psu.edu
We have previously demonstrated that 1-adrenergic (AR)-mediated contraction is diminished in the senescent rat heart, in part due to alterations in protein kinase C (PKC) signaling. Since chronic exercise training (EX) can exert independent effects on increasing 1-AR contraction in the adult rat heart, we sought to determine whether age-related defects in 1-AR contraction could be reversed by chronic EX. We further hypothesized that improved 1-AR contraction by EX may be PKC dependent. Adult (4 months; Y) and aged (24 months; O) male F344 rats were treadmill-trained (n = 1213/group; TR) at 70% of VO2max for 12 weeks or remained sedentary (YSED, YTR, OSED, OTR). Training status was verified by plantaris citrate synthase activity and left ventricular (LV) contractile responses (dP/dt) to 1-AR stimulation were assessed in Langendorff-perfused hearts using the 1-AR agonist phenylephrine (PE; 105 M) with and without the PKC inhibitor chelerythrine (CE; 106 M). 1-AR stimulation elicited greater increases in LV dP/dt in hearts isolated from OTR (4525.4 ± 224.1 mmHg/s) versus OSED (3658.9 ± 291.0 mmHg/s), while CE abolished PE-induced effects (OTR, 4069.2 ± 341.2) versus (OSED, 3608.9 ± 321.2) (p <.01). Upon western blotting, phosphospecific antibodies directed at PKC (pSer729) revealed greater levels in LV isolated from YTR versus YSED, and EX ameliorated aged-related reductions in OSED (p <.001). Basal PKC mRNA levels were also greater in YTR and OTR versus YSED (p <.01). PE-induced increases in phosphor-PKC (pThr507) levels observed in OSED were attenuated in OTR (p <.03). Chronic EX was also associated with significant reductions in PKC (pSer657) levels following PE in OTR (p <.002). The results indicate that age-related reductions in 1-AR contraction can be partially reversed by EX in the rat heart. These results further suggest that alterations in PKC levels underlie, at least in part, EX-induced improvements in 1-AR contraction.
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