[Mechanism of negative inotropic effect of tumor necrosis factor-alpha on rat myocardium].
To investigate the mechanism of the negative inotropic effect of tumor necrosis factor-alpha (TNF-alpha) in cardiomyocytes.



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.



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.



TNF-alpha decreases the myocardial contractility, at least partly, by inhibiting the activity of SR Ca(2+)- ATPase.
Fu
Chen
C
Department of Physiology, College of Medical Sciences, Zhejiang University, Hangzhou 310031, China.
Cao
Chun-mei
CM
Zhang
Jing
J
Xia
Qiang
Q
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium