Chronic exercise improves myocardial inotropic reserve capacity through α 1 -adrenergic and protein kinase C-dependent effects in senescent Rats

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We have previously demonstrated that α 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 α 1 -AR contraction in the adult rat heart, we sought to determine whether age-related defects in α 1 -AR contraction could be reversed by chronic EX. We further hypothesized that improved α 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 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 α 1 -AR stimulation were assessed in Langendorff-perfused hearts using the α 1 -AR agonist phenylephrine (PE; 10 -5 M) with and without the PKC inhibitor chelerythrine (CE; 10 -6 M). α 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 PKCε (pSer 729 ) 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 (pThr 507 ) levels observed in OSED were attenuated in OTR (p < .03). Chronic EX was also associated with significant reductions in PKCα (pSer 657 ) levels following PE in OTR (p < .002). The results indicate that age-related reductions in α 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 α 1 -AR contraction.

Original languageEnglish (US)
Pages (from-to)1089-1098
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume59
Issue number11
DOIs
StatePublished - Jan 1 2004

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Adrenergic Agents
Protein Kinase C
Phospho-Specific Antibodies
Citrate (si)-Synthase
Adrenergic Agonists
Protein C Inhibitor
Inbred F344 Rats
Phenylephrine
Protein Kinase Inhibitors
Western Blotting
Exercise
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Aging
  • Geriatrics and Gerontology

Cite this

@article{76a1fa97193242dbbbdfcef46b05fd52,
title = "Chronic exercise improves myocardial inotropic reserve capacity through α 1 -adrenergic and protein kinase C-dependent effects in senescent Rats",
abstract = "We have previously demonstrated that α 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 α 1 -AR contraction in the adult rat heart, we sought to determine whether age-related defects in α 1 -AR contraction could be reversed by chronic EX. We further hypothesized that improved α 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 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 α 1 -AR stimulation were assessed in Langendorff-perfused hearts using the α 1 -AR agonist phenylephrine (PE; 10 -5 M) with and without the PKC inhibitor chelerythrine (CE; 10 -6 M). α 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 PKCε (pSer 729 ) 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 (pThr 507 ) levels observed in OSED were attenuated in OTR (p < .03). Chronic EX was also associated with significant reductions in PKCα (pSer 657 ) levels following PE in OTR (p < .002). The results indicate that age-related reductions in α 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 α 1 -AR contraction.",
author = "Korzick, {Donna Hope} and Hunter, {James C.} and McDowell, {Mark K.} and Delp, {Michael D.} and Tickerhoof, {Marlena M.} and Carson, {La Toya D.}",
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Chronic exercise improves myocardial inotropic reserve capacity through α 1 -adrenergic and protein kinase C-dependent effects in senescent Rats . / Korzick, Donna Hope; Hunter, James C.; McDowell, Mark K.; Delp, Michael D.; Tickerhoof, Marlena M.; Carson, La Toya D.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 59, No. 11, 01.01.2004, p. 1089-1098.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chronic exercise improves myocardial inotropic reserve capacity through α 1 -adrenergic and protein kinase C-dependent effects in senescent Rats

AU - Korzick, Donna Hope

AU - Hunter, James C.

AU - McDowell, Mark K.

AU - Delp, Michael D.

AU - Tickerhoof, Marlena M.

AU - Carson, La Toya D.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - We have previously demonstrated that α 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 α 1 -AR contraction in the adult rat heart, we sought to determine whether age-related defects in α 1 -AR contraction could be reversed by chronic EX. We further hypothesized that improved α 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 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 α 1 -AR stimulation were assessed in Langendorff-perfused hearts using the α 1 -AR agonist phenylephrine (PE; 10 -5 M) with and without the PKC inhibitor chelerythrine (CE; 10 -6 M). α 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 PKCε (pSer 729 ) 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 (pThr 507 ) levels observed in OSED were attenuated in OTR (p < .03). Chronic EX was also associated with significant reductions in PKCα (pSer 657 ) levels following PE in OTR (p < .002). The results indicate that age-related reductions in α 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 α 1 -AR contraction.

AB - We have previously demonstrated that α 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 α 1 -AR contraction in the adult rat heart, we sought to determine whether age-related defects in α 1 -AR contraction could be reversed by chronic EX. We further hypothesized that improved α 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 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 α 1 -AR stimulation were assessed in Langendorff-perfused hearts using the α 1 -AR agonist phenylephrine (PE; 10 -5 M) with and without the PKC inhibitor chelerythrine (CE; 10 -6 M). α 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 PKCε (pSer 729 ) 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 (pThr 507 ) levels observed in OSED were attenuated in OTR (p < .03). Chronic EX was also associated with significant reductions in PKCα (pSer 657 ) levels following PE in OTR (p < .002). The results indicate that age-related reductions in α 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 α 1 -AR contraction.

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