In Vitro Endotoxin Exposure Induces Contractile Dysfunction in Adult Rat CardiacMyocytes

摘要

Tao, Shiying, and Thomas M. McKenna. In vitro endo- toxin exposure inducescontractile dysfunction in adult rat cardiac myocytes. Am. J. Physiol. 267 (Heart Circ. Physiol. 36): 111745-111752, 1994.-In vivo endotoxin treatment causes a nitric oxide-mediated hypocontractility in cardiac myocytes. The objective of this study was to assess whether in vitro endotoxin exposure confers similar contractile defects in adult rat cardiac cells. We found that incubation of cardiac myocytes for 6 h with 10-100 ng/ml endotoxin resulted in progressive time- and protein synthesis-dependent decreases in electrically stimulated twitch magnitudes and increased contraction and relaxation times. Serum was not required for the endotoxin-induced hypocontractility. The endotoxin-induced defect in contractility was reversed over time, since myocytes continuously incubated with endotoxin for 24 h exhibited normal contractility; in contrast, control cells incubated for 18 h were suppressed by a subsequent 6-h exposure to endotoxin. Nitric oxide synthase activity was increased after a 6-h endotoxin treatment as evidenced by a dose-dependent enhanced conversion of (3H)arginine to(3H)citrulline and by elevated guanosine 3'-5'-cydic monophosphate levels. Superfusion of endotoxin-incubated cells with N(w)-nitro-L-arginine methyl ester