Heart failure reduces both the effects and interaction between cyclic GMP and cyclic AMP

Jacob Moalem1, Harvey R Weiss, Tomer Davidov

  • 1Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA.

Insights

Cyclic AMP lessens cyclic GMP's negative effects in healthy hearts, but this protective interaction is diminished in heart hypertrophy and failure. This finding is crucial for understanding cardiac function in disease states.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Biochemistry

Background:

  • Cyclic guanosine monophosphate (cGMP) exerts negative functional effects on the heart.
  • Cyclic adenosine monophosphate (cAMP) is hypothesized to attenuate these cGMP effects.
  • This interaction may be impaired in pathological cardiac conditions like hypertrophy and failure.

Purpose of the Study:

  • To investigate the interaction between cyclic AMP and cyclic GMP in regulating cardiac function.
  • To determine if pacing-induced cardiac hypertrophy and failure alter this cAMP-cGMP interaction.
  • To assess the functional and metabolic consequences of these cyclic nucleotides in normal and failing hearts.

Main Methods:

  • Infusion of 8-bromo-cGMP and isoproterenol into the coronary arteries of control, hypertrophic (HYP), and hypertrophic failure (HYP-FAIL) dogs.
  • Measurement of regional myocardial work and oxygen consumption (VO(2)).
  • Determination of cyclic GMP and cyclic AMP levels via radioimmunoassay.

Main Results:

  • 8-bromo-cGMP decreased myocardial work and VO(2) in control dogs, but not in HYP or HYP-FAIL groups.
  • Isoproterenol increased work and VO(2) in control and HYP dogs, but decreased them in HYP-FAIL dogs.
  • Cyclic AMP levels were elevated by isoproterenol in control and HYP dogs, and further increased by 8-bromo-cGMP in controls, but not in HYP-FAIL dogs.

Conclusions:

  • Cyclic AMP attenuates the negative functional and metabolic effects of cyclic GMP in healthy hearts.
  • This protective interaction between cyclic AMP and cyclic GMP is significantly blunted in cardiac hypertrophy and failure.
  • The impaired interaction suggests a mechanism contributing to the functional decline in hypertrophic and failing hearts.
Abstract

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