Mechanism of negative inotropic effect of tumor necrosis factor-alpha on rat myocardium / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanism of the negative inotropic effect of tumor necrosis factor-alpha (TNF-alpha) in cardiomyocytes.</p><p><b>METHODS</b>The spectrofluorometric method was used to verify the calcium handling of the single myocyte. The activities of Ca(2+)-ATPase of sarcoplasmic reticulum (SR) and the activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase of plasma membrane were measured with colorimetric methods.</p><p><b>RESULTS</b>TNF-alpha at 20 U/ml and 200 U/ml depressed the contractility of ventricular papillary muscle to 91% and 76% of control (P<0.01) respectively, but had no effect on the amplitude of electrically induced calcium transient in single myocyte. TNF-alpha inhibited the responsiveness of SR Ca(2+)ATPase activity to ATP (0.1 - 4 mmol/L) and Ca(2+) (1 - 40 micromol/L). TNF-alpha did not alter the activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase of plasma membrane compared with control group.</p><p><b>CONCLUSION</b>TNF-alpha decreases the myocardial contractility, at least partly, by inhibiting the activity of SR Ca(2+)- ATPase.</p>