Nitrite and myocardial ischaemia reperfusion injury. Where are we now?

Research output: Contribution to journalArticlepeer-review

Authors

Colleges, School and Institutes

External organisations

  • University of Southampton
  • University of East Anglia

Abstract

Cardiovascular disease remains the leading cause of death worldwide despite major advances in technology and treatment, with coronary heart disease (CHD) being a key contributor. Following an acute myocardial infarction (AMI), it is imperative that blood flow is rapidly restored to the ischaemic myocardium. However, this restoration is associated with an increased risk of additional complications and further cardiomyocyte death, termed myocardial ischaemia reperfusion injury (IRI). Endogenously produced nitric oxide (NO) plays an important role in protecting the myocardium from IRI. It is well established that NO mediates many of its downstream functions through the ‘canonical’ NO-sGC-cGMP pathway, which is vital for cardiovascular homeostasis; however, this pathway can become impaired in the face of inadequate delivery of necessary substrates, in particular L-arginine, oxygen and reducing equivalents. Recently, it has been shown that during conditions of ischaemia an alternative pathway for NO generation exists, which has become known as the ‘nitrate–nitrite–NO pathway’. This pathway has been reported to improve endothelial dysfunction, protect against myocardial IRI and attenuate infarct size in various experimental models. Furthermore, emerging evidence suggests that nitrite itself provides multi-faceted protection, in an NO-independent fashion, against a myriad of pathophysiologies attributed to IRI. In this review, we explore the existing pre-clinical and clinical evidence for the role of nitrate and nitrite in cardioprotection and discuss the lessons learnt from the clinical trials for nitrite as a perconditioning agent. We also discuss the potential future for nitrite as a pre-conditioning intervention in man.

Bibliographic note

Funding Information: This work was funded by the British Heart Foundation ( PG/19/87/34792 ) to M.M., M.P.F., and M.F.

Details

Original languageEnglish
Article number107819
JournalPharmacology & Therapeutics
Volume223
Early online date15 Feb 2021
Publication statusPublished - Jul 2021

Keywords

  • Ischaemia reperfusion injury, Nitrate, Nitric oxide, Nitrite

ASJC Scopus subject areas

Sustainable Development Goals