title: The effect of insulin-like growth factor-1 on adult rat cardiac contractility.
abstract: 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-1 on isometric force development in isolated rat cardiac muscle and on intracellular calcium (Ca2+) handling in isolated cardiac myocytes. IGF-1 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.
authors.affiliation: Department of Neurobiology, Babraham Institute, Cambridge, UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Freestone
authors.forename: S
authors.initials: S
authors.lastname: Ribaric
authors.forename: W T
authors.initials: WT
authors.lastname: Mason
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D007211:Indoles; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007537:Isometric Contraction; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
chemical_list: D015220:Calcium Channels; D007211:Indoles; D007328:Insulin; D007334:Insulin-Like Growth Factor I; C048960:indo-1; D002118:Calcium