Chronic exercise improves myocardial inotropic reserve capacity through α1-adrenergic and protein kinase C-dependent effects in senescent Rats

Donna H. Korzick, James C. Hunter, Mark K. McDowell, Michael D. Delp, Marlena M. Tickerhoof, La Toya D. Carson

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We have previously demonstrated that α1-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 α1-AR contraction in the adult rat heart, we sought to determine whether age-related defects in α1-AR contraction could be reversed by chronic EX. We further hypothesized that improved α1-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 α1-AR stimulation were assessed in Langendorff-perfused hearts using the α1-AR agonist phenylephrine (PE; 10-5 M) with and without the PKC inhibitor chelerythrine (CE; 10-6 M). α1-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 PKCε (pSer729) revealed greater levels in LV isolated from YTR versus YSED, and EX ameliorated aged-related reductions in YSED (p < .001). Basal PKCε mRNA levels were also greater in YTR and OTR versus YSED (p < .01). PE-induced increases in phosphor-PKCδ (pThr507) levels observed in OSED were attenuated in OTR (p < .03). Chronic EX was also associated with significant reductions in PKCα (pSer657) levels following PE in OTR (p < .002). The results indicate that age-related reductions in α1-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 α1-AR contraction.

Original languageEnglish (US)
Pages (from-to)1089-1098
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number11
StatePublished - Nov 2004

All Science Journal Classification (ASJC) codes

  • Aging
  • Geriatrics and Gerontology


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