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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Negative inotropic effects of cytokines on the heart mediated by nitric oxide.

The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.[1]


  1. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Finkel, M.S., Oddis, C.V., Jacob, T.D., Watkins, S.C., Hattler, B.G., Simmons, R.L. Science (1992) [Pubmed]
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