TY - JOUR
T1 - Chronic exercise improves myocardial inotropic reserve capacity through α1-adrenergic and protein kinase C-dependent effects in senescent Rats
AU - Korzick, Donna H.
AU - Hunter, James C.
AU - McDowell, Mark K.
AU - Delp, Michael D.
AU - Tickerhoof, Marlena M.
AU - Carson, La Toya D.
N1 - Funding Information:
ACKNOWLEDGMENTS The Three-City Study is conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen-Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The Three-City study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MutualitéGénérale de l’Éducation Nationale (MGEN), Institut de la Longévité, Conseils Régionaux d’Aquitaine et Bourgogne, Fondation de France, and Ministry of Research-INSERM Programme ‘‘Cohortes et collections de données biologiques.’’ J. A. Ávila-Funes was supported by a Bourse Charcot (2006–2007) from the Ministère des Affaires Étrangères in France.
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
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U2 - 10.1093/gerona/59.11.1089
DO - 10.1093/gerona/59.11.1089
M3 - Article
C2 - 15602054
AN - SCOPUS:11144328191
SN - 1079-5006
VL - 59
SP - 1089
EP - 1098
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 11
ER -