Increased contribution of α1- vs. β-adrenoceptor-mediated inotropic response in rats with congestive heart failure

  1. I. Sjaastad1,
  2. I. Schiander2,
  3. A. Sjetnan2,
  4. E. Qvigstad2,
  5. J. Bøkenes1,
  6. D. Sandnes2,
  7. J.-B. Osnes2,
  8. O. M. Sejersted1,
  9. T. Skomedal2

Article first published online: 21 MAR 2003

DOI: 10.1046/j.1365-201X.2003.01063.x

Issue

Acta Physiologica Scandinavica

Acta Physiologica Scandinavica

Volume 177, Issue 4, pages 449–458, April 2003

Additional Information

How to Cite

Sjaastad, I., Schiander, I., Sjetnan, A., Qvigstad, E., Bøkenes, J., Sandnes, D., Osnes, J.-B., Sejersted, O. M. and Skomedal, T. (2003), Increased contribution of α1- vs. β-adrenoceptor-mediated inotropic response in rats with congestive heart failure. Acta Physiologica Scandinavica, 177: 449–458. doi: 10.1046/j.1365-201X.2003.01063.x

Author Information

  1. 1

     Institute for Experimental Medical Research, University of Oslo, Ullevaal University Hospital, Oslo, Norway

  2. 2

     Department of Pharmacology, University of Oslo, Oslo, Norway

* T. Skomedal, Department of Pharmacology, University of Oslo, PO Box 1057 Blindern, N-0316 Oslo, Norway.

Publication History

  1. Issue published online: 21 MAR 2003
  2. Article first published online: 21 MAR 2003
  3. Received 3 February 2002, accepted 6 November 2002

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Keywords:

  • adrenoceptors;
  • contractile function;
  • heart failure;
  • inotropy;
  • lusitropy;
  • myocardium

Abstract

Aim:  In failing myocardium the mechanical response to β-adrenoceptor stimulation is attenuated. Alternative signalling systems might provide inotropic support when the β-adrenoceptor system is dysfunctioning. Accordingly, the inotropic responses to α1- and β-adrenoceptor stimulation by the endogenous adrenoceptor agonist noradrenaline in non-failing and failing rat hearts were compared.

Methods:  Chronic heart failure was induced in male Wistar rats by coronary artery ligation. Corresponding sham groups were prepared. After 6 weeks, papillary muscles from non-failing and failing hearts were isolated. Receptor binding studies were performed in the corresponding myocardium. The α1-adrenoceptor-mediated inotropic response was not changed while the β-adrenoceptor-mediated response was substantially reduced in failing compared with non-failing myocardium.

Results:  No change in potency for the agonists was observed at the α1-adrenoceptors, while an increased potency for the agonists at the β-adrenoceptors was found during heart failure. The lusitropic response to β-adrenoceptor stimulation was intact during heart failure. No over all change in affinity or number of either adrenoceptor type was observed in receptor binding studies. The α1-adrenoceptor-mediated inotropic response became dominating compared with the β-adrenoceptor-mediated one in failing rat myocardium in contrast to the dominating role of the latter in non-failing myocardium. The attenuation of the β-adrenoceptor-mediated inotropic response in rat failing myocardium was not because of a reduced number of receptors.

Conclusion:  Increasing contractility through stimulation of α1-adrenoceptors in situ by the endogenous agonist may be an alternative way of inotropic support during heart failure and even more so during β-adrenoceptor blockade.

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