[Involvement of nitric oxide in the effect of interleukin-2 on the contractility of rat ventricular cardiomyocytes].
The aim of the present study was to investigate the effect of interleukin-2 (IL-2) on the contractility in cardiomyocytes and the underlying mechanisms. Ventricular myocytes were isolated from adult male Sprague-Dawley rats. Contractile responses were evaluated by use of the video tracking system. Contractile parameters in cardiomyocytes electrically stimulated at 0.2 Hz included peak velocity of cell shortening (+dL/dtmax), peak velocity of cell relengthening (-dL/dtmax), contractile amplitude (dL), and end-diastolic cell length. Calcium transients of ventricular myocytes were determined by the spectrofluorometric techniques. Dose-dependent inhibition in + dL/dtmax, -dL/dtmax, dL and end-diastolic cell length were induced by IL-2 at 2-1000 U/ml. Pretreatment with the nitric oxide synthase inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L) and soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo [4,3a]quinoxalin-1-one (ODQ, 10 micromol/L) attenuated IL-2-induced inhibition of contractility. Aminoguanidine, an inhibitor of inducible nitric oxide synthase, had no effect on the inhibition by IL-2. IL-2 at 200 U/ml decreased the amplitude of electrically induced [Ca2+]i transients of ventricular myocytes. Pretreatment with ODQ diminished IL-2-induced inhibition of amplitude of the calcium transient. In conclusion, the present study indicates a direct action of IL-2 on cardiomyocyte contraction, possibly through an increased NO production, activation of soluble guanylyl cyclase and inhibition in intracellular Ca2+ level.
Wang
Hui Ping
HP
Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031.
Xia
Qiang
Q
Cao
Chun Mei
CM
Lu
Yuan
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats
D007376:Interleukin-2; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester