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  • Title: Chronic exercise improves myocardial inotropic reserve capacity through alpha1-adrenergic and protein kinase C-dependent effects in Senescent rats.
    Author: Korzick DH, Hunter JC, McDowell MK, Delp MD, Tickerhoof MM, Carson LD.
    Journal: J Gerontol A Biol Sci Med Sci; 2004 Nov; 59(11):1089-98. PubMed ID: 15602054.
    Abstract:
    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 approximately 70% of VO(2max) 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 PKCepsilon (pSer(729)) revealed greater levels in LV isolated from YTR versus YSED, and EX ameliorated aged-related reductions in OSED (p < .001). Basal PKCepsilon mRNA levels were also greater in YTR and OTR versus YSED (p < .01). PE-induced increases in phosphor-PKCdelta (pThr(507)) levels observed in OSED were attenuated in OTR (p < .03). Chronic EX was also associated with significant reductions in PKCalpha (pSer(657)) 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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