Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases

J Intern Med. 2016 Apr;279(4):315-36. doi: 10.1111/joim.12441. Epub 2015 Nov 2.


Nitric oxide (NO) is generated endogenously by NO synthases to regulate a number of physiological processes including cardiovascular and metabolic functions. A decrease in the production and bioavailability of NO is a hallmark of many major chronic diseases including hypertension, ischaemia-reperfusion injury, atherosclerosis and diabetes. This NO deficiency is mainly caused by dysfunctional NO synthases and increased scavenging of NO by the formation of reactive oxygen species. Inorganic nitrate and nitrite are emerging as substrates for in vivo NO synthase-independent formation of NO bioactivity. These anions are oxidation products of endogenous NO generation and are also present in the diet, with green leafy vegetables having a high nitrate content. The effects of nitrate and nitrite are diverse and include vasodilatation, improved endothelial function, enhanced mitochondrial efficiency and reduced generation of reactive oxygen species. Administration of nitrate or nitrite in animal models of cardiovascular disease shows promising results, and clinical trials are currently ongoing to investigate the therapeutic potential of nitrate and nitrite in hypertension, pulmonary hypertension, peripheral artery disease and myocardial infarction. In addition, the nutritional aspects of the nitrate-nitrite-NO pathway are interesting as diets suggested to protect against cardiovascular disease, such as the Mediterranean diet, are especially high in nitrate. Here, we discuss the potential therapeutic opportunities for nitrate and nitrite in prevention and treatment of cardiovascular and metabolic diseases.

Keywords: beetroot; blood pressure; ischaemia; nitric oxide; vasodilatation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Availability
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / prevention & control
  • Cardiovascular System / drug effects
  • Disease Models, Animal
  • Heart Failure / drug therapy
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Leukocytes / drug effects
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / prevention & control
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / metabolism
  • Nitrates / metabolism
  • Nitrates / therapeutic use*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / biosynthesis
  • Nitrites / metabolism
  • Nitrites / therapeutic use*
  • Platelet Activation / drug effects
  • Reperfusion Injury / drug therapy
  • Vasodilation / drug effects


  • Nitrates
  • Nitrites
  • Nitric Oxide
  • Nitric Oxide Synthase