title: Malfunction of vascular control in lifestyle-related diseases: formation of systemic hemoglobin-nitric oxide complex (HbNO) from dietary nitrite.
abstract: Nitric oxide (NO) has many physiological functions. It is believed to be produced from L-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are waste forms of it. By the way, nitrate and nitrite are abundant in vegetables and fruits, especially leafy vegetables and pickled vegetables. Orally-ingested nitrate is changed to nitrite by micro-organelles living in the hypopharynx area, and nitrite is expected to change to NO in the stomach due to its low pH. Indeed, some researchers reported that NO is produced in the gastric cavity, although few reports mentioned the physiological meanings of this NO formation. Therefore, we investigated whether the nitrite-derived NO can shift to the circulation and acts like NOS-derived NO does in tissues. We adopted a stable isotope of nitrite (15NO2-) in order to distinguish between the endogenous nitrite and the exogenously administered one and measured nitrosyl hemoglobin (HbNO) as an index of circulating NO using electron paramagnetic resonance spectroscopy. It appeared that the oral administration of 15N-nitrite formed the Hb15NO in rat blood and decreased the blood pressure of chronic L-NAME treated rats. Our findings suggest that the intake of nitrite (or nitrate)-rich foods such as vegetables and fruits would alter the systemic HbNO dynamism, resulting in the improvement of cardiovascular diseases.
authors.affiliation: Department of Clinical Pharmacology, Subdivision of Clinical Pharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima Graduate School, 1-78 Sho-machi, Tokushima 770-8505, Japan. tsuchiya@ph.tokushima-u.ac.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Masumi
authors.initials: M
authors.lastname: Okamoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izawa
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kanematsu
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D006454:Hemoglobins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D051381:Rats
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester