Elevated Afterload, Neuroendocrine Stimulation, and Human Heart Failure Increase BNP Levels and Inhibit Preload-Dependent SERCA Upregulation
2008 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Elevated Afterload, Neuroendocrine Stimulation, and Human Heart Failure Increase BNP Levels and Inhibit Preload-Dependent SERCA Upregulation
Toischer, K. ; Koegler, H.; Tenderich, G.; Grebe, C.; Seidler, T. ; Van, P. N. & Jung, K. et al. (2008)
Circulation: Heart Failure, 1(4) pp. 265-271. DOI: https://doi.org/10.1161/CIRCHEARTFAILURE.108.785279
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- Authors
- Toischer, Karl ; Koegler, Harald; Tenderich, Gero; Grebe, Cornelia; Seidler, Tim ; Van, Phuc Nguyen; Jung, Klaus ; Knoell, Ralph; Koerfer, Reiner; Hasenfuß, Gerd
- Abstract
- Background-In heart failure, brain-type natriuretic peptide (BNP) is elevated and the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) downregulated. We previously showed that preload-induced SERCA-upregulation is suppressed by exogenous BNP. Methods and Results-Here we tested the hypothesis that afterload and neurohumoral activation would counterregulate preload-dependent SERCA upregulation through BNP, which finally results in decreased SERCA levels. We studied the effects of 6 hours preload, afterload, and isoproterenol stimulation on BNP and SERCA mRNA expression in rabbit and human failing muscles strips. Preload resulted in a pronounced upregulation of SERCA by 149% (isotonic versus slack, P<0.01). This upregulation was largely suppressed in afterloaded muscles (isometric versus slack: +32%; P<0.05). Similarly, presence of isoproterenol prevented SERCA upregulation in isotonic muscles. Afterload and isoproterenol resulted in a pronounced increase in BNP expression compared with slack by 225% (P<0.05) and 198% (P<0.01), respectively. Isoproterenol also increased expression of phospholamban by 84% (P<0.0 1). SERCA upregulation in preloaded muscles is associated with frequency-dependent potentiation of contractile force, which is absent in afterloaded muscles. In failing human myocardium, BNP expression was upregulated compared with nonfailing (+631%; P<0.05). Neither unloading nor preload or afterload induced a change in SERCA or BNP expression after 6 hours. Conclusions-Afterload and neuroendocrine stimulation increase BNP expression thereby causing inhibition of preload-dependent SERCA upregulation. In failing human myocardium, high BNP expression may underlie the loss of preload-dependent upregulation of SERCA. BNP may thus contribute to adverse myocardial remodelling in heart failure. (Circ Heart Fail. 2008;1:265-271.)
- Issue Date
- 2008
- Publisher
- Lippincott Williams & Wilkins
- Journal
- Circulation: Heart Failure
- ISSN
- 1941-3289