title: Chronic exercise improves myocardial inotropic reserve capacity through alpha1-adrenergic and protein kinase C-dependent effects in Senescent rats.
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.
authors.affiliation: 106 Noll Physiological Research Center, The Pennsylvania State University, University Park, PA 16802, USA. dhk102@psu.edu
authors.forename: Donna H
authors.initials: DH
authors.lastname: Korzick
authors.forename: James C
authors.initials: JC
authors.lastname: Hunter
authors.forename: Mark K
authors.initials: MK
authors.lastname: McDowell
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
authors.forename: Marlena M
authors.initials: MM
authors.lastname: Tickerhoof
authors.forename: Latoya D
authors.initials: LD
authors.lastname: Carson
mesh_terms: D000375:Aging / Q000502:physiology*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects; D010617:Phenanthridines / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D015398:Signal Transduction; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C016299:chelerythrine; D002950:Citrate (si)-Synthase; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3