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Insulin-like growth factor-1 but not growth hormone augments mammalian myocardial contractility by sensitizing the myofilament to Ca2+ through a wortmannin-sensitive pathway: studies in rat and ferret isolated muscles.

Publication ,  Journal Article
Cittadini, A; Ishiguro, Y; Strömer, H; Spindler, M; Moses, AC; Clark, R; Douglas, PS; Ingwall, JS; Morgan, JP
Published in: Circ Res
July 13, 1998

A growing body of evidence has been accumulated recently suggesting that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) affect cardiac function, but their mechanism(s) of action is unclear. In the present study, GH and IGF-1 were administered to isolated isovolumic aequorin-loaded rat whole hearts and ferret papillary muscles. Although GH had no effect on the indices of cardiac function, IGF-1 increased isovolumic developed pressure by 24% above baseline. The aequorin transients were abbreviated and demonstrated decreased amplitude. The positive inotropic effects of IGF-1 were not associated with increased intracellular Ca2+ availability to the contractile machinery but to a significant increase of myofilament Ca2+ sensitivity. Accordingly, the Ca2+-force relationship obtained under steady-state conditions in tetanized muscle was shifted significantly to the left (EC50, 0.44+/-0.02 versus 0.52+/-0.03 micromol/L with and without IGF-1 in the perfusate, respectively; P<0.05); maximal Ca2+-activated tetanic pressure was increased significantly by 12% (211+/-3 versus 235+/-2 mm Hg in controls and IGF-1-treated hearts, respectively; P<0.01). The positive inotropic actions of IGF-1 were not associated with changes in either pHi or high-energy phosphate content, as assessed by 31P nuclear magnetic resonance spectroscopy, and were blocked by the phosphatidylinositol 3-kinase inhibitor wortmannin. Concomitant administration of IGF binding protein-3 blocked IGF-1-positive inotropic action in ferret papillary muscles. In conclusion, IGF-1 is an endogenous peptide that through a wortmannin-sensitive pathway displays distinct positive inotropic properties by sensitizing the myofilaments to Ca2+ without increasing myocyte [Ca2+]i.

Duke Scholars

Published In

Circ Res

DOI

ISSN

0009-7330

Publication Date

July 13, 1998

Volume

83

Issue

1

Start / End Page

50 / 59

Location

United States

Related Subject Headings

  • Wortmannin
  • Rats, Sprague-Dawley
  • Rats
  • Papillary Muscles
  • Myocardial Contraction
  • Male
  • Magnetic Resonance Spectroscopy
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Protein 3
  • In Vitro Techniques
 

Citation

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Cittadini, A., Ishiguro, Y., Strömer, H., Spindler, M., Moses, A. C., Clark, R., … Morgan, J. P. (1998). Insulin-like growth factor-1 but not growth hormone augments mammalian myocardial contractility by sensitizing the myofilament to Ca2+ through a wortmannin-sensitive pathway: studies in rat and ferret isolated muscles. Circ Res, 83(1), 50–59. https://doi.org/10.1161/01.res.83.1.50
Cittadini, A., Y. Ishiguro, H. Strömer, M. Spindler, A. C. Moses, R. Clark, P. S. Douglas, J. S. Ingwall, and J. P. Morgan. “Insulin-like growth factor-1 but not growth hormone augments mammalian myocardial contractility by sensitizing the myofilament to Ca2+ through a wortmannin-sensitive pathway: studies in rat and ferret isolated muscles.Circ Res 83, no. 1 (July 13, 1998): 50–59. https://doi.org/10.1161/01.res.83.1.50.

Published In

Circ Res

DOI

ISSN

0009-7330

Publication Date

July 13, 1998

Volume

83

Issue

1

Start / End Page

50 / 59

Location

United States

Related Subject Headings

  • Wortmannin
  • Rats, Sprague-Dawley
  • Rats
  • Papillary Muscles
  • Myocardial Contraction
  • Male
  • Magnetic Resonance Spectroscopy
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Protein 3
  • In Vitro Techniques