title: Nitrite signaling in pulmonary hypertension: mechanisms of bioactivation, signaling, and therapeutics.
abstract: CONCLUSIONS
  Pulmonary arterial hypertension (PAH) is a disorder characterized by increased pulmonary vascular resistance and mean pulmonary artery pressure leading to impaired function of the right ventricle, reduced cardiac output, and death. An imbalance between vasoconstrictors and vasodilators plays an important role in the pathobiology of PAH.
  
  
  BACKGROUND
  Nitric oxide (NO) is a potent vasodilator in the lung, whose bioavailability and signaling pathway are impaired in PAH. It is now appreciated that the oxidative product of NO metabolism, the inorganic anion nitrite (NO(2)(-)), functions as an intravascular endocrine reservoir of NO bioactivity that can be reduced back to NO under physiological and pathological hypoxia.
  
  
  RESULTS
  The conversion of nitrite to NO is controlled by coupled electron and proton transfer reactions between heme- and molybdenum-containing proteins, such as hemoglobin and xanthine oxidase, and by simple protonation and disproportionation, and possibly by catalyzed disproportionation. The two major sources of nitrite (and nitrate) are the endogenous L-arginine-NO pathway, by oxidation of NO, and the diet, with conversion of nitrate from diet into nitrite by oral commensal bacteria. In the current article, we review the enzymatic formation of nitrite and the available data regarding its use as a therapy for PAH and other cardiovascular diseases.
  
  
  CONCLUSIONS
  The successful efficacy demonstrated in several animal models and safety in early clinical trials suggest that nitrite may represent a promising new therapy for PAH.
authors.affiliation: Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Bueno
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mora
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
mesh_terms: D000818:Animals; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism* / Q000627:therapeutic use; D015398:Signal Transduction; D014652:Vascular Diseases / Q000188:drug therapy / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide