title: Does central nitric oxide chronically modulate the acute hypoxic ventilatory response in conscious rats?
abstract: OBJECTIVE
  Hypoxia initiates an increase in ventilation (VE) through a cascade of events of which central nitric oxide (NO) has been implicated as an important neuromodulator. There have not been any reports describing the consequences of long-term imbalances in the central NO pathways on the modulation of the acute hypoxic ventilatory response (HVR). Chronic hypoxia (CH) can potentially modify the HVR, and so we hypothesized that central NO may be involved. In this study we describe the long-term role of central NO in the modulation of HVR before and after CH.
  
  
  METHODS
  Male Sprague-Dawley rats (BW c. 200-320 g; n = 21) were implanted with an osmotic pump for continuous intracerebroventricular administration of either artificial cerebrospinal fluid (control), Nomega-nitro-L-arginine methyl ester (L-NAME) (150 microg kg(-1) day(-1)) or the NO-donor, 3-[4-morpholinyl]-sydnonimine-hydrochloride (SIN-1) (100 microg kg(-1) day(-1)). The VE response to acute poikilocapnic hypoxia (8% O2 for 20 min) was measured by plethysmography seven days after surgery, in normoxia, and again after 14 days of exposure to CH (CH = 12% O2).
  
  
  RESULTS
  The magnitude of the HVR (c. 230% increase in VE) was unaltered by centrally infusing either L-NAME or SIN-1 for 1 week. CH did not modify the HVR, although baseline VE and HVR were shifted downward by L-NAME during CH - because of a reduction in the frequency component.
  
  
  CONCLUSIONS
  These results suggest that long-term alterations in central NO levels may not alter the HVR under moderate CH, presumably because of the onset/development of compensatory mechanisms. However, NO appears to be an important component of the HVR following CH.
authors.affiliation: Department of Biochemistry, National Cardiovascular Center Research Institute, Suita, Osaka, Japan. schwenke@ri.ncvc.go.jp
authors.forename: D O
authors.initials: DO
authors.lastname: Schwenke
authors.forename: J T
authors.initials: JT
authors.lastname: Pearson
authors.forename: K
authors.initials: K
authors.lastname: Kangawa
authors.forename: M
authors.initials: M
authors.lastname: Shirai
mesh_terms: D000208:Acute Disease; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects*
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester