Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bisping, E; Tenderich, G; Barckhausen, P; Stumme, B; Bruns, S; von Lewinski, D; Pieske, B.
Atrial myocardium is the predominant inotropic target of adrenomedullin in the human heart.
Am J Physiol Heart Circ Physiol. 2007; 293(5):H3001-H3007
Doi: 10.1152/ajpheart.01276.2006
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- Führende Autor*innen der Med Uni Graz
- Bisping Egbert Hubertus
- Pieske Burkert Mathias
- Co-Autor*innen der Med Uni Graz
- von Lewinski Dirk
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- Abstract:
- Adrenomedullin (ADM) is an endogenous peptide with favorable hemodynamic effects in vivo. In this study, we characterized the direct functional effects of ADM in isolated preparations from human atria and ventricles. In electrically stimulated human nonfailing right atrial trabeculae, ADM (0.0001-1 micromol/l) increased force of contraction in a concentration-dependent manner, with a maximal increase by 35 +/- 8% (at 1 micromol/l; P < 0.05). The positive inotropic effect was accompanied by a disproportionate increase in calcium transients assessed by aequorin light emission [by 76 +/- 20%; force/light ratio (DeltaF/DeltaL) 0.58 +/- 0.15]. In contrast, elevation of extracellular calcium (from 2.5 to 3.2 mmol/l) proportionally increased force and aequorin light emission (DeltaF/DeltaL 1.0 +/- 0.1; P < 0.05 vs. ADM). Consistent with a cAMP-dependent mechanism, ADM (1 micromol/l) increased atrial cAMP levels by 90 +/- 12%, and its inotropic effects could be blocked by the protein kinase A (PKA) inhibitor H-89. ADM also exerted positive inotropic effects in failing atrial myocardium and in nonfailing and failing ventricular myocardium. The inotropic response was significantly weaker in ventricular vs. atrial myocardium and in failing vs. nonfailing myocardium. In conclusion, ADM exerts Ca(2+)-dependent positive inotropic effects in human atrial and less-pronounced effects in ventricular myocardium. The inotropic effects are related to increased cAMP levels and stimulation of PKA. In heart failure, the responsiveness to ADM is reduced in atria and ventricles.
- Find related publications in this database (using NLM MeSH Indexing)
- Adrenomedullin - administration and dosage
- Cardiotonic Agents -
- Dose-Response Relationship, Drug -
- Heart Atria -
- Humans -
- Myocardial Contraction - drug effects
- Ventricular Dysfunction, Left - physiopathology
- Find related publications in this database (Keywords)
- contractility
- Ca2+ handling
- human myocardium