Brain stem NO modulates ventilatory acclimatization to hypoxia in mice

Area of Science:

• Physiology
• Neuroscience
• Respiratory Medicine

Background:

• Neuronal nitric oxide synthase (nNOS) plays a role in physiological processes.
• Ventilatory acclimatization to hypoxia is a complex adaptation.
• The involvement of nNOS in hypoxic ventilatory response and acclimatization requires further investigation.

Purpose of the Study:

• To assess the role of neuronal nitric oxide synthase (nNOS) in ventilatory acclimatization to hypoxia.
• To investigate the impact of nNOS inhibition on ventilation in acclimatized mice.
• To examine the expression of NMDA glutamate receptor and nNOS in response to chronic hypoxia.

Main Methods:

• Bl6/CBA mice were exposed to chronic hypoxia or normoxia for 2 weeks.
• Ventilation was measured under normoxic and hypoxic conditions before and after nNOS inhibitor treatment.
• Medulla tissue was analyzed for nitric oxide (NO) metabolites, nNOS, and NMDA receptor expression (mRNA and protein) using RT-PCR and Western blot.

Main Results:

• Chronic hypoxia increased ventilation, which was attenuated by nNOS inhibition.
• nNOS inhibition primarily reduced tidal volume in normoxia and acute hypoxia.
• Hypoxia induced increased expression of NMDA receptors, nNOS, and NO production in the medulla.

Conclusions:

• nNOS activation is involved in ventilatory acclimatization to hypoxia in mice.
• nNOS is not essential for the acute hypoxic ventilatory response.
• Increased NMDA receptor expression in the medulla contributes to the acute hypoxic ventilatory response in chronically hypoxic mice.
• Central nervous system plasticity, involving nNOS, partially mediates ventilatory acclimatization to hypoxia.