THE EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I ON ADULT-RAT CARDIAC CONTRACTILITY

There is increasing evidence that insulin-like growth factor-1 (IGF-1) may play a role in both physiological and pathophysiological events i n the mammalian myocardium. The present study investigated the acute e ffects of IGF-1 on isometric force development in isolated rat cardiac muscle and on intracellular calcium (Ca2+) handling in isolated cardi ac 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 papill ary muscles by 56.7 +/- 7.7% at a concentration of 100 nM (n = 22). In comparison, insulin increased papillary muscle force development by 1 1.6 +/- 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 ampli tude 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 i n free, peak cytosolic Ca2+ in isolated cardiac myocytes. Increasing i nsulin 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 IG F-1 may act on the mammalian myocardium when administered chronically, but this study is amongst the first to demonstrate an acute effect of IGF-1 on the mammalian heart. IGF-1 may prove then to be a novel card ioactive agent in both normal and pathophysiological states.