The effect of insulin-like growth factor-1 on adult rat cardiac contractility
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- Freestone, N.S., Ribaric, S. & Mason, W.T. Mol Cell Biochem (1996) 163: 223. doi:10.1007/BF00408662
There is increasing evidence that insulin-like growth factor-1 (IGF-1) may play a role in both physiological and pathophysiological events in the mammalian myocardium. The present study investigated the acute effects of IGF-I on isometric force development in isolated rat cardiac muscle and on intracellular calcium (Ca2+) handling in isolated cardiac myocytes. IGF-I had a positive inotropic effect on rat ventricular papillary muscles increasing force development by 17.8 ± 4.6%, 18.5 ± 5.8% and 11.9 ± 4.9% (n = 12–20) at concentrations of 1, 10 and 100 ng/ml respectively. Isoprenaline increased tension in these papillary muscles by 56.7 ± 7.7% at a concentration of 100 nM (n = 22). In comparison, insulin increased papillary muscle force development by 11.6 ± 3.2%, 17.7 ± 4.1% and 19.7 ± 5.6% at concentrations of 1, 10 and 100 nM respectively (n = 16–20). In the single cardiac myocyte IGF-1 increased, the peak cytosolic free Ca2+ concentration, the amplitude of the Ca2+ transient and the time to peak Ca2+ as measured with the fluorescent bioprobe Indo-1 AM. The positive inotropic response to IGF-1 by rat ventricular muscle is therefore associated with a rise in free, peak cytosolic Ca2+ in isolated cardiac myocytes. Increasing insulin concentrations (1–1000 nM) elicited a progressive elevation in isometric force and free, cytosolic Ca2+. In contrast, in the presence of IGF-1, the maximal rise in isometric force and free cytosolic Ca2+ were both observed at 10 ng/ml. Recent reports have suggested that IGF-1 may act on the mammalian myocardium when administered chronically, but this study is amongst the first to demonstrate an acute effect of IGF-I on the mammalian heart. IGF-1 may prove then to be a novel cardioactive agent in both normal and pathophysiological states.
Key wordsIGF-I cardiac myocytes inotropic calcium fluorescence isometric force
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