title: Platelet inhibition and increased phosphorylated vasodilator-stimulated phosphoprotein following sodium nitrite inhalation.
abstract: In the presence of red blood cells (RBCs), nitrite inhibits platelets through its conversion to nitric oxide (NO) by the reductase activity of partially deoxygenated hemoglobin. Inhaled sodium nitrite is being investigated as a therapy for pulmonary hypertension. Here, we measured platelet aggregation, P-selectin expression, platelet-leukocyte aggregates and phosphorylated vasodilator-stimulated phosphoprotein (P-VASPSer239) following sodium nitrite inhalation in healthy subjects. In vitro incubation of nitrite with deoxygenated whole blood showed an increase in P-VASPSer239, which was inhibited by ODQ, a soluble guanylyl cyclase (sGC) inhibitor. Immediately and 60 min after nitrite inhalation, P-VASPSer239increased in platelets. Platelet aggregation, P-selectin expression, platelet-monocyte and platelet-lymphocyte aggregates decreased after inhalation. In conclusion, sodium nitrite administered to healthy subjects by inhalation can inhibit platelet activation and increase P-VASPSer239in platelets. Platelet inhibition by nitrite administration may be useful in disorders associated with platelet hyperactivity.
authors.affiliation: Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand; Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Tipparat
authors.initials: T
authors.lastname: Parakaw
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Kran
authors.initials: K
authors.lastname: Suknuntha
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Pornpun
authors.initials: P
authors.lastname: Vivithanaporn
authors.affiliation: Department of General Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Schlagenhauf
authors.affiliation: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Supachai
authors.initials: S
authors.lastname: Topanurak
authors.affiliation: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.affiliation: Center of Excellence for Flow Cytometry, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Kovit
authors.initials: K
authors.lastname: Pattanapanyasat
authors.affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Schechter
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Nathawut
authors.initials: N
authors.lastname: Sibmooh
authors.affiliation: Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand. Electronic address: sirada.srh@mahidol.ac.th.
authors.forename: Sirada
authors.initials: S
authors.lastname: Srihirun
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000378:metabolism; D010750:Phosphoproteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000494:pharmacology*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D009573:Nitrites; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D009569:Nitric Oxide; D012977:Sodium Nitrite; D010100:Oxygen
keywords: Deoxygenation; Inhaled nitrite; Nitric oxide; Platelets; Vasodilator-stimulated phosphoprotein