Leptin attenuates cardiac contraction in rat ventricular myocytes - Role of NO

Obesity is commonly associated with impaired myocardial contractile functio n. However, a direct link between these 2 states has not yet been establish ed. There has been an indication that leptin, the product of the human obes ity gene, may play a role in obesity-related metabolic and cardiovascular d ysfunctions. The purpose of this study was to determine whether leptin exer ts any direct cardiac contractile action that may contribute to altered myo cardial function. Ventricular myocytes were isolated from adult male Spragu e-Dawley rats. Contractile responses were evaluated by use of video-based e dge detection. Contractile properties analyzed in cells electrically stimul ated at 0.5 Hz included peak shortening, time to 90% peak shortening, time to 90% relengthening, and fluorescence intensity change. Leptin exhibited a dose-dependent inhibition in myocyte shortening and intracellular Ca2+ cha nge, with maximal inhibitions of 22.4% and 26.2%, respectively. Pretreatmen t with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-N AME, 100 mu mol/L) blocked leptin-induced inhibition of both peak shortenin g and fluorescence intensity change. Leptin also stimulated NO synthase act ivity in a time- and concentration-dependent manner, as reflected in the do se-related increase in NO accumulation in these cells. Addition of an NO do nor (S-nitroso-N-acetyl-penicillamine [SNAP]) to the medium mimicked the ef fects of leptin administration. In summary, this study demonstrated a direc t action of leptin on cardiomyocyte contraction, possibly through an increa sed NO production. These data suggest that leptin may play a role in obesit y-related cardiac contractile dysfunction.