Related Experiment Video
Updated: Aug 9, 2026

Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)
Published on: July 3, 2025
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.
Background:
We tested the hypothesis that the negative functional effects of cyclic GMP would be attenuated by cyclic AMP and this interaction would be reduced in pacing-induced failure of hypertrophic hearts.
Materials And Methods:
8-Bromo-cGMP (2 microg/kg/min) was infused into a coronary artery in eight control, eight ventricular hypertrophy (HYP), and eight hypertrophic failure (HYP-FAIL) dogs. Then isoproterenol (0.1 microg/kg/min) was infused, followed by 8 Br-cGMP. Regional myocardial work (force*shortening/min), and O(2) consumption (VO(2)) (coronary blood flow*O(2) extraction) were measured. Cyclic GMP levels were determined by radioimmunoassay.
Results:
8-Br-cGMP significantly decreased regional work from 3812 +/- 839 g*mm/min by 17% and VO(2) by 29% in control, but not in HYP (1073 +/- 182 by -10%, VO(2) by -16%) or HYP-FAIL (495 +/- 145 by -9%, VO(2) by 0%). Isoproterenol increased work by 43% and VO(2) by 48% in controls and in HYP (work by 54%, VO(2) by 39%), but not in HYP-FAIL (work by -28%, VO(2) by -5%). Subsequently, 8-Br-cGMP had no effect on work or VO(2) in control (-2%, -13%), HYP (-12%, -30%), or HYP-FAIL (+13%, +14%). Cyclic AMP levels were elevated by isoproterenol in control (381 +/- 115 versus 553 +/- 119 pmol/g) and HYP (313 +/- 55 versus 486 +/- 227), but not in HYP-FAIL (300 +/- 60 versus 284 +/- 126). After isoproterenol, 8-Br-cGMP further elevated cyclic AMP in control (687 +/- 122), but not in HYP or HYP-FAIL.
Conclusions:
In controls, cyclic AMP attenuated cyclic GMPs negative functional and metabolic effects. The effects and the interaction were blunted in the HYP and HYP-FAIL groups.
Related Concept Videos
G-Protein Gated Ion Channels
Sensory organs,...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Heart Failure Drugs: Inotropic Agents
Heart Failure Drugs: β-Blockers
Pathophysiology of Heart Failure
Heart Failure II: Pathophysiology
