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Inotropic responses to phosphodiesterase inhibitors in cardiac hypertrophy in rats

Oleg Osadchii1, Gavin Norton, Angela Woodiwiss

  • 1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg 2193, South Africa. woodiwissaj@physiology.wits.ac.za

European Journal of Pharmacology
|May 25, 2005
PubMed

Insights

Cardiac hypertrophy preserves contractile responses to phosphodiesterase inhibitors, even with reduced beta-adrenergic signaling. This suggests alternative therapeutic targets for heart failure.

Area of Science:

  • Cardiovascular Physiology
  • Pharmacology

Background:

  • Chronic cardiac hypertrophy often involves beta-adrenergic inotropic downregulation.
  • The impact of this downregulation on responses to phosphodiesterase (PDE) inhibitors is not fully understood.

Purpose of the Study:

  • To investigate if contractile responses to PDE inhibitors are reduced in chronic cardiac hypertrophy with beta-adrenergic downregulation.
  • To compare PDE inhibitor efficacy in normal versus hypertrophic heart preparations.

Main Methods:

  • Isolated, isovolumically contracting heart preparations from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) control rats.
  • Assessment of inotropic responses to isoproterenol (beta-adrenoceptor agonist), PDE inhibitors (amrinone, milrinone, rolipram, pentoxifylline), and a cAMP analogue (8-Br-cAMP).

Main Results:

  • SHR exhibited significantly reduced inotropic responses to isoproterenol compared to WKY rats.
  • Contractile responses to PDE III, PDE IV, and non-selective PDE inhibitors were similar in both SHR and WKY hearts.
  • The inotropic potency of 8-Br-cAMP was increased in SHR.

Conclusions:

  • Contractile responses to phosphodiesterase inhibitors are preserved in chronic cardiac hypertrophy despite beta-adrenergic downregulation.
  • PDE inhibitors may represent a viable therapeutic strategy for heart failure associated with this condition.

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