title: No evidence of a role for neuronal nitric oxide synthase in the nucleus tractus solitarius in ventilatory responses to acute or chronic hypoxia in awake rats.
abstract: When exposed to a hypoxic environment, the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR and is termed ventilatory acclimatization to hypoxia (VAH). This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. The mechanisms of HVR plasticity are currently poorly understood. We hypothesized that changes in neuronal nitric oxide synthase (nNOS) activity or expression in the nucleus tractus solitarius contribute to this plasticity and underlie VAH in rats. To test this, we treated rats held in normoxia or 10% O2 (CSH, PIO2 = 70 Torr) for 7-9 days and measured ventilation in conscious, unrestrained animals before and after microinjecting the general NOS antagonist L-NG-Nitroarginine methyl ester into the nucleus tractus solitarius (NTS) or systemically injecting the nNOS-specific antagonist S-methyl-l-thiocitrulline. Localization of injection sites in the NTS was confirmed by histology following the experiment. We found that 1) neither NTS-specific nor systemic nNOS antagonism had any effect on hypoxia-mediated changes in breathing or metabolism (P > 0.05), but 2) nNOS protein expression was increased in the middle and caudal NTS by CSH. A persistent HVR after nNOS blockade in the NTS contrasts with results in awake mice, and our findings do not support the hypotheses that nNOS in the NTS contribute to the HVR or VAH in awake rats.
authors.affiliation: Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California; and Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Pamenter
authors.affiliation: Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Ariel
authors.initials: A
authors.lastname: Go
authors.affiliation: Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California; and fpowell@ucsd.edu.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Powell
mesh_terms: D000064:Acclimatization / Q000502:physiology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014691:Ventilation / Q000379:methods; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D002956:Citrulline; D052248:Nitric Oxide Synthase Type I; D013890:Thiourea; C086717:S-methylthiocitrulline; D019331:NG-Nitroarginine Methyl Ester
keywords: chronic sustained hypoxia; hypoxic ventilatory response; plethysmography; synaptic plasticity