Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 59:1089-1098 (2004)
© 2004 The Gerontological Society of America

Chronic Exercise Improves Myocardial Inotropic Reserve Capacity Through {alpha}1-Adrenergic and Protein Kinase C-Dependent Effects in Senescent Rats

Donna H. Korzick1,2,, James C. Hunter1, Mark K. McDowell1, Michael D. Delp3, Marlena M. Tickerhoof1,2 and LaToya D. Carson1,2

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 {alpha}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 {alpha}1-AR contraction in the adult rat heart, we sought to determine whether age-related defects in {alpha}1-AR contraction could be reversed by chronic EX. We further hypothesized that improved {alpha}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 = 12–13/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 {alpha}1-AR stimulation were assessed in Langendorff-perfused hearts using the {alpha}1-AR agonist phenylephrine (PE; 10–5 M) with and without the PKC inhibitor chelerythrine (CE; 10–6 M). {alpha}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{varepsilon} (pSer729) revealed greater levels in LV isolated from YTR versus YSED, and EX ameliorated aged-related reductions in OSED (p <.001). Basal PKC{varepsilon} mRNA levels were also greater in YTR and OTR versus YSED (p <.01). PE-induced increases in phosphor-PKC{delta} (pThr507) levels observed in OSED were attenuated in OTR (p <.03). Chronic EX was also associated with significant reductions in PKC{alpha} (pSer657) levels following PE in OTR (p <.002). The results indicate that age-related reductions in {alpha}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 {alpha}1-AR contraction.




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F. BATTAINI and A. PASCALE
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Ann. N.Y. Acad. Sci., December 1, 2005; 1057(1): 177 - 192.
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