Negative Inotropic Effect of Interleukin-2 in the Isolated Ventricular Myocytes: Role of NO/sGC Pathway

The present study is to investigate the effect and possible mechanism of interleukin-2 (IL-2) on the cell contractility in isolated rat cardiomyocytes. Ventricular myocytes were isolated from adult male Sprague-Dawley rats. Contractile responses were evaluated by use of the video tracking system. Contractile properties analyzed in cells electrically stimulated at 0.2Hz included peak velocity of cell shortening (+dL/dtmax), peak velocity of cell relengthening (-dL/dtmax), contraction amplitude (dL) and end-diastolic cell length. Calcium transients of ventricular myocytes were determined by the spectrofluorometric techniques. IL-2 (2.0, 10, 50, 200 and 1000 U/ml) exhibited a dose-dependent inhibition in +dL/dtmax, -dL/dtmax, dL and end-diastolic cell length. Pretreatment with the nitric oxide synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME, 100 microM) and 1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor) blocked IL-2-induced inhibition of the contract 2+ ility. IL-2 at 200U/ml decreased the amplitude of the [Ca ]itransient. Pretreatment with the L-NAME or ODQ abolished IL-2-induced inhibition of amplitude of the calcium transient. We conclude that the depressant effect of IL-2 on the contraction and calcium transient of isolated ventricular myocytes is mediated by nitric oxide/soluble guanylyl cyclase pathway.