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Negative Inotropic Effects of Cytokines on the Heart Mediated by Nitric Oxide
Abstract
The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor α, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor N G -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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Citations
Cited by
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Widlansky, M. E., Gokce, N., Keaney, J. F., & Vita, J. A. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(03)00994-x · Cited by 1,749
Bozkurt, B., Kribbs, S. B., Clubb, F. J., Michael, L. H., Didenko, V. V., Hornsby, P. J., Seta, Y., Oral, H., Spinale, F. G., & Mann, D. L. (1998) · Circulation · doi:10.1161/01.cir.97.14.1382 · Cited by 821
The nitric oxide and cGMP signal transduction system: regulation and mechanism of action
Schmidt, H. H. H. W., Lohmann, S. M., & Walter, U. (1993) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(93)90006-b · Cited by 746
Thyroid hormones and cardiovascular disease
Jabbar, A., Pingitore, A., Pearce, S. H. S., Zaman, A., Iervasi, G., & Razvi, S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.174 · Cited by 729
Expression of Inducible Nitric Oxide Synthase in Human Heart Failure
Haywood, G. A., Tsao, P. S., von der Leyen, H. E., Mann, M. J., Keeling, P. J., Trindade, P. T., Lewis, N. P., Byrne, C. D., Rickenbacher, P. R., Bishopric, N. H., et al. (1996) · Circulation · doi:10.1161/01.cir.93.6.1087 · Cited by 490
Metadata
- Authors
- Finkel, M. S., Oddis, C. V., Jacob, T. D., Watkins, S. C., Hattler, B. G., & Simmons, R. L.
- Venue
- Science
- Published
- 1992-07-17
- Volume
- 257
- Issue
- 5068
- Pages
- 387-389
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2019951936
- Cited by
- 1,628
- References
- 0
- FWCI
- 36.76
- Type
- journal article
- Language
- en
- Open access
- closed
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- Finkel, M. S., Oddis, C. V., Jacob, T. D., Watkins, S. C., Hattler, B. G., & Simmons, R. L. (1992). Negative Inotropic Effects of Cytokines on the Heart Mediated by Nitric Oxide. Science. https://doi.org/10.1126/science.1631560
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