Strategies to increase nitric oxide signalling in cardiovascular disease

Nat Rev Drug Discov. 2015 Sep;14(9):623-41. doi: 10.1038/nrd4623. Epub 2015 Aug 7.


Nitric oxide (NO) is a key signalling molecule in the cardiovascular, immune and central nervous systems, and crucial steps in the regulation of NO bioavailability in health and disease are well characterized. Although early approaches to therapeutically modulate NO bioavailability failed in clinical trials, an enhanced understanding of fundamental subcellular signalling has enabled a range of novel therapeutic approaches to be identified. These include the identification of: new pathways for enhancing NO synthase activity; ways to amplify the nitrate-nitrite-NO pathway; novel classes of NO-donating drugs; drugs that limit NO metabolism through effects on reactive oxygen species; and ways to modulate downstream phosphodiesterases and soluble guanylyl cyclases. In this Review, we discuss these latest developments, with a focus on cardiovascular disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / therapy*
  • Humans
  • Nitric Oxide / metabolism*
  • Reactive Oxygen Species / metabolism
  • Risk Reduction Behavior
  • Signal Transduction / physiology*


  • Reactive Oxygen Species
  • Nitric Oxide