Ca2+ sensitization and PKC contribute to exercise training-enhanced contractility in porcine collateral-dependent coronary arteries

Juan Carlos Robles, Michael Sturek, Janet L. Parker, Cristine L. Heaps

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Exercise training enhances endothelium-dependent coronary vasodilatation, improving perfusion and contractile function of collateral-dependent myocardium. Paradoxically, studies from our laboratory have revealed increased Ca2+-dependent basal active tone in collateral-dependent arteries of exercise-trained pigs. In this study, we tested the hypothesis that exercise training enhances agonist-mediated contractile responses of collateral-dependent arteries by promoting Ca2+ sensitization. Ameroid constrictors were surgically placed around the proximal left circumflex coronary (LCX) artery of female Yucatan miniature pigs. Eight weeks postoperatively, pigs were randomized into sedentary (pen confined) or exercise-training (treadmill run; 5 days/wk; 14 wk) groups. Arteries (~150 (μm luminal diameter) were isolated from the collateral-dependent and nonoccluded (left anterior descending artery supplied) myocardial regions, and measures of contractile tension or simultaneous tension and intracellular free Ca2+ concentration levels (fura-2) were completed. Exercise training enhanced contractile responses to endothelin-1 in collateral-dependent compared with nonoccluded arteries, an effect that was more pronounced in the presence of nitric oxide synthase inhibition (Nω-nitro-L-arginine methyl ester; 100 μM). Contractile responses to endothelin-1 were not altered by coronary occlusion alone. Exercise training produced increased tension at comparable levels of intracellular free Ca2+ concentration in collateral-dependent compared with nonoccluded arteries, indicative of exercise training-enhanced Ca2+ sensitization. Inhibition of PKC (calphostin C; 1 (μM), but not Rho-kinase (Y-27632, 10 μM; or hydroxyfasudil, 30 (μM), abolished the training-enhanced endothelin-1-mediated contractile response. Exercise training also increased sensitivity to the PKC activator phorbol 12,13-dibutyrate in collateral-dependent compared with nonoccluded arteries. Taken together, these data reveal that exercise training enhances endothelin-1-mediated contractile responses in collateral-dependent coronary arteries likely via increased PKC-mediated Ca2+ sensitization.

Original languageEnglish (US)
Pages (from-to)H1201-H1209
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Coronary artery disease
  • Coronary circulation
  • Endothelin
  • Protein kinase C
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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