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A Pacing-Controlled Procedure for the Assessment of Heart Rate-Dependent Diastolic Functions in Murine Heart Failure Models
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Published on: July 21, 2023

Modulation of cGMP in heart failure: a new therapeutic paradigm

Guido Boerrigter1, Harald Lapp, John C Burnett

  • 1Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Heart and Lung Research Center, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Handbook of Experimental Pharmacology
|December 18, 2008
PubMed

Insights

Novel therapeutic strategies for heart failure (HF) focus on augmenting cyclic guanosine monophosphate (cGMP) signaling. Targeting nitric oxide/soluble guanylate cyclase (NO/sGC) and natriuretic peptide/GC-A (NP/GC-A) pathways offers promising approaches for HF treatment.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Heart failure (HF) presents significant morbidity and mortality, necessitating innovative therapeutic interventions.
  • Cyclic guanosine monophosphate (cGMP) acts as a crucial second messenger in cardiovascular signaling pathways regulated by distinct guanylate cyclases (GCs).
  • Both the nitric oxide/soluble GC (NO/sGC) and natriuretic peptide/GC-A (NP/GC-A) systems are impaired in HF, indicating potential for therapeutic enhancement.

Purpose of the Study:

  • To explore novel therapeutic strategies for heart failure by targeting cGMP signaling pathways.
  • To review current and emerging approaches for augmenting NO/sGC and NP/GC-A systems in cardiovascular disease.
  • To highlight the potential of phosphodiesterase inhibition as an additional strategy to enhance cGMP signaling.

Main Methods:

  • Review of existing literature on NO/sGC activators, natriuretic peptides, and phosphodiesterase inhibitors in the context of heart failure.
  • Analysis of the mechanisms underlying cGMP dysregulation in HF.
  • Discussion of novel therapeutic agents currently in clinical development.

Main Results:

  • Conventional nitrovasodilators activate sGC but have limitations including cGMP-independent actions and tolerance development.
  • Novel NO-independent sGC activators are in development and lack these limitations.
  • Emerging strategies include GC-A activation via natriuretic peptides and inhibition of NP-degrading enzymes.
  • Inhibition of phosphodiesterase 5 offers another route to boost cGMP signaling.

Conclusions:

  • Augmenting cGMP signaling pathways represents a key therapeutic avenue for heart failure.
  • NO-independent sGC activators, natriuretic peptide-based therapies, and phosphodiesterase inhibitors offer distinct strategies to address HF.
  • Further clinical development of these agents is warranted to improve outcomes for HF patients.

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