title: It is rocket science - why dietary nitrate is hard to 'beet'! Part I: twists and turns in the realization of the nitrate-nitrite-NO pathway.
abstract: Dietary nitrate (found in green leafy vegetables, such as rocket, and in beetroot) is now recognized to be an important source of nitric oxide (NO), via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. While this pathway may now seem obvious, its realization followed a rather tortuous course over two decades. Early steps included the discovery that nitrite was a source of NO in the ischaemic heart but this appeared to have deleterious effects. In addition, nitrate-derived nitrite provided a gastric source of NO. However, residual nitrite was not thought to be absorbed systemically. Nitrite was also considered to be physiologically inert but potentially carcinogenic, through N-nitrosamine formation. In Part 1 of a two-part Review on the nitrate-nitrite-NO pathway we describe key twists and turns in the elucidation of the pathway and the underlying mechanisms. This provides the critical foundation for the more recent developments in the nitrate-nitrite-NO pathway which are covered in Part 2.
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas, Hospital, London, SE1 7EH, UK.
authors.forename: Jibran
authors.initials: J
authors.lastname: Khatri
authors.affiliation: Department of Dietetics and Nutrition, Division of Diabetes and Nutritional Sciences, King's College London, London, SE1 0NH, UK.
authors.forename: Charlotte Elizabeth
authors.initials: CE
authors.lastname: Mills
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas, Hospital, London, SE1 7EH, UK.
authors.forename: Perry
authors.initials: P
authors.lastname: Maskell
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas, Hospital, London, SE1 7EH, UK.
authors.forename: Chimed
authors.initials: C
authors.lastname: Odongerel
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas, Hospital, London, SE1 7EH, UK.
authors.forename: Andrew James
authors.initials: AJ
authors.lastname: Webb
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control*; D038441:Diet, Mediterranean; D006801:Humans; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide
keywords: blood pressure; dietary nitrate; endothelial function; ischaemia-reperfusion; nitrite; platelets