Nitric oxide signaling in the cardiovascular system: Implications for heart failure

Roberto M. Saraiva, Joshua M. Hare

Research output: Contribution to journalArticlepeer-review


PURPOSE OF REVIEW: The role played by nitric oxide (NO) in cardiovascular physiology remains highly controversial. Following the discovery that NO is the prototypic endothelium-derived relaxing factor, this signaling molecule was implicated as possessing many other biological actions within the cardiovascular system, including effects on cardiac contraction, relaxation, and energetics. Here, we discuss new concepts regarding NO signaling, its effector pathways, and interactions between NO and the redox milieu within a framework of cardiac physiology and pathophysiology. RECENT FINDINGS: Major recent insights that have advanced understanding of the mechanisms of NO bioactivity include the following. (1) NO acts in subcellular signaling compartments or modules. (2) S-nitrosylation (covalent modification of cysteine thiol moieties) of proteins represents a prototypic second messenger signaling mode in biologic systems. (3) Reactive oxygen and nitrogen species work together to facilitate signaling. (4) Disruption of physiologic signaling can occur by either increased formation of reactive oxygen species or decreased production of reactive nitrogen species, a situation of nitroso-redox imbalance. SUMMARY: These insights, which challenge classically held views that NO acts as a freely diffusible molecule regulated primarily by concentration and exerting signaling primarily through cyclic GMP production, offer a new perspective on the pathophysiology and treatment of congestive heart failure.

Original languageEnglish (US)
Pages (from-to)221-228
Number of pages8
JournalCurrent Opinion in Cardiology
Issue number3
StatePublished - May 2006


  • Heart failure
  • Nitric oxide
  • Nitric oxide synthase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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