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

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.