TNF-α Rapidly Antagonizes the β-Adrenergic Responses of the Chloride Current in Guinea-Pig Ventricular Myocytes

Kenji Iino, Hiroyuki Watanabe, Takashi Saito, Satoshi Kibira, Toshihiko Iijima, Mamoru Miura
2003 Circulation Journal  
umor necrosis factor-alpha (TNF-) is a proinflammatory cytokine with a broad range of pleiotropic effects. 1 The adult human heart expresses both mRNA and receptor proteins for type I and type II TNFreceptors. 2 TNF-is also expressed de novo by cardiac myocytes after certain forms of stress 3 and plays a fundamental role in various pathophysiological conditions, including acute myocarditis, myocardial infarction, sepsisassociated cardiac dysfunction, and advanced congestive heart failure. [4]
more » ... eart failure. [4] [5] [6] [7] It seems likely that different processes are responsible for the early and late cardiac effects of TNF-. 8,9 Excessive production of inducible nitric oxide synthase (iNOS) has been shown to cause the late onset of functional depression in the heart, 9-11 but the mechanisms underlying the early onset of cardiac depression remain controversial. Finkel et al postulated that TNF-depressed contractility of isolated papillary muscles within 5 min and that the effects were reversed by NG-monomethyl-L-arginine, speculating that the early cardiodepressant effects of TNFwere mediated by a constitutive NOS (cNOS) action in the myocardium. 12 Krown et al have reported that TNFrapidly inhibits the basal L-type Ca 2+ current and contrac-
doi:10.1253/circj.67.347 pmid:12655167 fatcat:bf6xgjaz5fgwzoibnjt4qth7pu