The cardiovascular response in sepsis: proposed mechanisms of the beneficial effect of adrenomedullin and its binding protein (Review)

  • Authors:
    • Dale E. Fowler
    • Ping Wang
  • View Affiliations

  • Published online on: May 1, 2002     https://doi.org/10.3892/ijmm.9.5.443
  • Pages: 443-449
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Abstract

Sepsis and its complications are leading causes of morbidity and mortality. A better understanding of the mechanisms responsible for the shift from the early, hyperdynamic phase of sepsis to the late hypodynamic phase could lead to novel therapies that might improve the outcome of the septic patient. Adrenomedullin is a vasodilatory peptide which shows sustained elevation starting early in sepsis and is important in initiating the hyperdynamic response. As sepsis progresses, however, the vascular response to adrenomedullin is blunted and this decreased sensitivity is important in producing the shift to the late, hypodynamic phase. The decline in the vascular response to adrenomedullin is related to a sepsis-induced decrease in the binding protein for adrenomedullin (i.e., adrenomedullin binding protein-1) rather than a change in gene expression of the components of adrenomedullin receptors. Treatment of septic animals with the combination of adrenomedullin and its binding protein prevents the transition to the late phase of sepsis, maintains cardiovascular stability, and reduces sepsis-induced mortality. We propose that the mechanisms responsible for the beneficial effect of adrenomedullin and adrenomedullin binding protein-1 in sepsis are associated with downregulation of proinflammatory cytokines (TNF-α, IL-1β, IL-6), maintainence of endothelial constitutive nitric oxide synthase, and reduction of vascular endothelial cell apoptosis.

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May 2002
Volume 9 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Fowler DE and Wang P: The cardiovascular response in sepsis: proposed mechanisms of the beneficial effect of adrenomedullin and its binding protein (Review). Int J Mol Med 9: 443-449, 2002.
APA
Fowler, D.E., & Wang, P. (2002). The cardiovascular response in sepsis: proposed mechanisms of the beneficial effect of adrenomedullin and its binding protein (Review). International Journal of Molecular Medicine, 9, 443-449. https://doi.org/10.3892/ijmm.9.5.443
MLA
Fowler, D. E., Wang, P."The cardiovascular response in sepsis: proposed mechanisms of the beneficial effect of adrenomedullin and its binding protein (Review)". International Journal of Molecular Medicine 9.5 (2002): 443-449.
Chicago
Fowler, D. E., Wang, P."The cardiovascular response in sepsis: proposed mechanisms of the beneficial effect of adrenomedullin and its binding protein (Review)". International Journal of Molecular Medicine 9, no. 5 (2002): 443-449. https://doi.org/10.3892/ijmm.9.5.443