title: The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans.
abstract: Platelets play an important role in the development of vascular disease, while vegetarian diets, which are rich in inorganic nitrate, protect against it. This study was performed to assess the effect of potassium nitrate (KNO(3)) ingestion on platelet function in humans. Oral KNO(3) (2 mmol) was given to healthy volunteers and its effect on platelet function assessed by measuring the aggregant effect of collagen. Blood samples were taken for measurement of plasma S-nitrosothiols (RSNO) and platelet cyclic GMP and nitrotyrosine levels. Gastric juice samples were taken for measurement of RSNO. In a separate study, the effect of oral KNO(3) on portal RSNO levels in patients with intrahepatic porto-systemic shunts was assessed. KNO(3) caused a significant increase in gastric RSNO levels, from 0.46 +/- 0.06 to 3.62 +/- 2.82 microM (t(max) 45 min; P < 0.001), and significantly inhibited platelet function (t(max) 60 min; P < 0.001). There was no effect on systemic or portal RSNO, platelet cGMP or platelet nitrotyrosine levels. Oral KNO(3) inhibits platelet aggregation. The time course suggests that gastric RSNO production may be involved in this effect. The protection against vascular events associated with a high intake of vegetables may be due to their high nitrate content.
authors.affiliation: Department of Clinical Pharmacology, St. Bartholomew's Hospital, Barts and the London, Queen Mary School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: G
authors.initials: G
authors.lastname: Richardson
authors.forename: S L
authors.initials: SL
authors.lastname: Hicks
authors.forename: S
authors.initials: S
authors.lastname: O'Byrne
authors.forename: M T
authors.initials: MT
authors.lastname: Frost
authors.forename: K
authors.initials: K
authors.lastname: Moore
authors.forename: N
authors.initials: N
authors.lastname: Benjamin
authors.forename: G M
authors.initials: GM
authors.lastname: McKnight
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D003094:Collagen / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D014676:Diet, Vegetarian; D005260:Female; D005750:Gastric Juice / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008297:Male; D009566:Nitrates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests; D026403:S-Nitrosothiols / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D009566:Nitrates; D026403:S-Nitrosothiols; C002744:3-nitrotyrosine; D014443:Tyrosine; D003094:Collagen; D006152:Cyclic GMP