title: Prolonged nitric oxide inhalation fails to regress hypoxic vascular remodeling in rat lung.
abstract: OBJECTIVE
  The purpose of present study was to investigate whether long-term nitric oxide (NO) inhalation during the recovery in air might improve the regression of chronic hypoxic pulmonary hypertension (PH) and vascular changes.
  
  
  METHODS
  The rats were exposed to 10 ppm of NO in air for 10 days (n = 12) and 30 days (n = 4), or 40 ppm of NO in air for 10 days (n = 6) and 30 days (n = 12) following 10 days of hypobaric hypoxia (380 mm Hg, 10% oxygen). For each NO group, air control rats following hypoxic exposure were studied at the same time (n = 13, 11, 9, and 11, respectively). Normal air rats (n = 6) without hypoxic exposure and rats (n = 7) following 10 days of hypoxic exposure were used as normal and chronic hypoxic control groups, respectively. Muscularization of normally nonmuscular peripheral arteries and medial hypertrophy of normally muscular arteries were assessed by light microscopy. An additional 16 rats were used to investigate the recovery of pulmonary artery pressure with (n = 8) and without NO inhalation (n = 8) after 10 days of hypobaric hypoxia.
  
  
  RESULTS
  Long-term hypoxia-induced PH, right ventricular hypertrophy (RVH), and hypertensive pulmonary vascular changes, each of which regressed partly after recovery in room air. There were no differences among rats with and without NO during each recovery period in RVH, medial wall thickness of muscular artery, and the percentages of muscularized arteries at the alveolar wall and duct levels. Continuous inhaled 40 ppm NO decreased pulmonary artery pressure from 40.1 +/- 1.1 to 29.9 +/- 3.8 mm Hg (mean +/- SE) [n = 8], which was not different in the rats without NO inhalation (n = 8). Urine nitrate level was higher in rats that had inhaled NO.
  
  
  CONCLUSIONS
  Continuous NO inhalation showed no effect on regression of pulmonary vascular remodeling in chronic hypoxic PH after returning to room air.
authors.affiliation: Department of Anesthesiology and the Intensive Care Unit, Faculty of Medicine, University of Mie, Japan.
authors.forename: Bao Hua
authors.initials: BH
authors.lastname: Jiang
authors.forename: Junko
authors.initials: J
authors.lastname: Maruyama
authors.forename: Ayumu
authors.initials: A
authors.lastname: Yokochi
authors.forename: Manabu
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Homare
authors.initials: H
authors.lastname: Amano
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mitani
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D017211:Treatment Failure; D014655:Vascular Resistance / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D009569:Nitric Oxide