PMID- 15599101 OWN - NLM STAT- MEDLINE DCOM- 20050428 LR - 20190911 IS - 1347-8613 (Print) IS - 1347-8613 (Linking) VI - 96 IP - 4 DP - 2004 Dec TI - Malfunction of vascular control in lifestyle-related diseases: formation of systemic hemoglobin-nitric oxide complex (HbNO) from dietary nitrite. PG - 395-400 AB - 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. FAU - Tsuchiya, Koichiro AU - Tsuchiya K AD - 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 FAU - Takiguchi, Yoshiharu AU - Takiguchi Y FAU - Okamoto, Masumi AU - Okamoto M FAU - Izawa, Yuki AU - Izawa Y FAU - Kanematsu, Yasuhisa AU - Kanematsu Y FAU - Yoshizumi, Masanori AU - Yoshizumi M FAU - Tamaki, Toshiaki AU - Tamaki T LA - eng PT - Journal Article PT - Review DEP - 20041210 PL - Japan TA - J Pharmacol Sci JT - Journal of pharmacological sciences JID - 101167001 RN - 0 (Hemoglobins) RN - 0 (Nitrites) RN - 31C4KY9ESH (Nitric Oxide) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Blood Pressure/drug effects MH - Diet MH - Dose-Response Relationship, Drug MH - Electron Spin Resonance Spectroscopy MH - Hemoglobins/*metabolism MH - Kidney/metabolism MH - Male MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Nitric Oxide/*metabolism MH - Nitrites/*metabolism MH - Rats RF - 56 EDAT- 2004/12/16 09:00 MHDA- 2005/04/29 09:00 CRDT- 2004/12/16 09:00 PHST- 2004/12/16 09:00 [pubmed] PHST- 2005/04/29 09:00 [medline] PHST- 2004/12/16 09:00 [entrez] AID - JST.JSTAGE/jphs/FMJ04006X3 [pii] AID - 10.1254/jphs.fmj04006x3 [doi] PST - ppublish SO - J Pharmacol Sci. 2004 Dec;96(4):395-400. doi: 10.1254/jphs.fmj04006x3. Epub 2004 Dec 10.