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Science 17 July 1992:
Vol. 257. no. 5068, pp. 387 - 389
DOI: 10.1126/science.1631560
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Articles

Science, Vol 257, Issue 5068, 387-389
Copyright © 1992 by American Association for the Advancement of Science

articles

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

MS Finkel, CV Oddis, TD Jacob, SC Watkins, BG Hattler, and RL Simmons

Department of Medicine, University of Pittsburgh School of Medicine, PA 15213.

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.


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ICAM-1 and VCAM-1 mediate endotoxemic myocardial dysfunction independent of neutrophil accumulation.
C. D. Raeburn, C. M. Calkins, M. A. Zimmerman, Y. Song, L. Ao, A. Banerjee, A. H. Harken, and X. Meng (2002)
Am J Physiol Regulatory Integrative Comp Physiol 283, R477-R486
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Neutralization of IL-18 attenuates lipopolysaccharide-induced myocardial dysfunction.
C. D. Raeburn, C. A. Dinarello, M. A. Zimmerman, C. M. Calkins, B. J. Pomerantz, R. C. McIntyre Jr., A. H. Harken, and X. Meng (2002)
Am J Physiol Heart Circ Physiol 283, H650-H657
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Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure.
T. Saito, F. Hu, L. Tayara, L. Fahas, H. Shennib, and A. Giaid (2002)
Am J Physiol Heart Circ Physiol 283, H339-H345
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Escherichia coli LPS-induced LV dysfunction: role of toll-like receptor-4 in the adult heart.